Targeting mutant KRAS
Curr Opin Chem Biol. 2021 Apr 7;62:101-108. doi: 10.1016/j.cbpa.2021.02.010. Online ahead of print.ABSTRACTThe protein KRAS has for decades been considered a holy grail of cancer drug discovery. For most of that time, it has also been considered undruggable. Since 2018, five compounds have entered the clinic targeting a single mutant form of KRAS, G12C. Here, we review each of these compounds along with additional approaches to targeting this and other mutants. Remaining challenges include expanding the identification of inhibitors to a broader range of known mutants and to conformations of the protein more likely to avoid...
Source: Current Opinion in Chemical Biology - April 10, 2021 Category: Biochemistry Authors: Daniel A Erlanson Kevin R Webster Source Type: research

Structures of chromatin modulators in complex with nucleosome
Curr Opin Chem Biol. 2021 Apr 3;63:105-114. doi: 10.1016/j.cbpa.2021.02.018. Online ahead of print.ABSTRACTThe chromatin structure is dynamically regulated by many different modulators that post-translationally modify histones, replace canonical histones with histone variants, and unwind nucleosomal DNA, thereby modulating the accessibility of nucleosomal DNA and facilitating downstream DNA-templated nuclear processes. To understand how these modulators change the chromatin structure, it is essential to determine the 3D structures of chromatin modulators in complex with nucleosome. Here, we review the very recent progress ...
Source: Current Opinion in Chemical Biology - April 6, 2021 Category: Biochemistry Authors: Jinrong Min Ke Liu Source Type: research

Structures of chromatin modulators in complex with nucleosome
Curr Opin Chem Biol. 2021 Apr 3;63:105-114. doi: 10.1016/j.cbpa.2021.02.018. Online ahead of print.ABSTRACTThe chromatin structure is dynamically regulated by many different modulators that post-translationally modify histones, replace canonical histones with histone variants, and unwind nucleosomal DNA, thereby modulating the accessibility of nucleosomal DNA and facilitating downstream DNA-templated nuclear processes. To understand how these modulators change the chromatin structure, it is essential to determine the 3D structures of chromatin modulators in complex with nucleosome. Here, we review the very recent progress ...
Source: Current Opinion in Chemical Biology - April 6, 2021 Category: Biochemistry Authors: Jinrong Min Ke Liu Source Type: research

Structures of chromatin modulators in complex with nucleosome
Curr Opin Chem Biol. 2021 Apr 3;63:105-114. doi: 10.1016/j.cbpa.2021.02.018. Online ahead of print.ABSTRACTThe chromatin structure is dynamically regulated by many different modulators that post-translationally modify histones, replace canonical histones with histone variants, and unwind nucleosomal DNA, thereby modulating the accessibility of nucleosomal DNA and facilitating downstream DNA-templated nuclear processes. To understand how these modulators change the chromatin structure, it is essential to determine the 3D structures of chromatin modulators in complex with nucleosome. Here, we review the very recent progress ...
Source: Current Opinion in Chemical Biology - April 6, 2021 Category: Biochemistry Authors: Jinrong Min Ke Liu Source Type: research

Structures of chromatin modulators in complex with nucleosome
Curr Opin Chem Biol. 2021 Apr 3;63:105-114. doi: 10.1016/j.cbpa.2021.02.018. Online ahead of print.ABSTRACTThe chromatin structure is dynamically regulated by many different modulators that post-translationally modify histones, replace canonical histones with histone variants, and unwind nucleosomal DNA, thereby modulating the accessibility of nucleosomal DNA and facilitating downstream DNA-templated nuclear processes. To understand how these modulators change the chromatin structure, it is essential to determine the 3D structures of chromatin modulators in complex with nucleosome. Here, we review the very recent progress ...
Source: Current Opinion in Chemical Biology - April 6, 2021 Category: Biochemistry Authors: Jinrong Min Ke Liu Source Type: research

The ubiquitin proteoform problem
Curr Opin Chem Biol. 2021 Apr 1;63:95-104. doi: 10.1016/j.cbpa.2021.02.015. Online ahead of print.ABSTRACTThe diversity of ubiquitin modifications is immense. A protein can be monoubiquitylated, multi-monoubiquitylated, and polyubiquitylated with chains varying in size and shape. Ubiquitin itself can be adorned with other ubiquitin-like proteins and smaller functional groups. Considering different combinations of post-translational modifications can give rise to distinct biological outcomes, characterizing ubiquitylated proteoforms of a given protein is paramount. In this Opinion, we review recent advances in detecting and...
Source: Current Opinion in Chemical Biology - April 4, 2021 Category: Biochemistry Authors: Kirandeep K Deol Eric R Strieter Source Type: research

The ubiquitin proteoform problem
Curr Opin Chem Biol. 2021 Apr 1;63:95-104. doi: 10.1016/j.cbpa.2021.02.015. Online ahead of print.ABSTRACTThe diversity of ubiquitin modifications is immense. A protein can be monoubiquitylated, multi-monoubiquitylated, and polyubiquitylated with chains varying in size and shape. Ubiquitin itself can be adorned with other ubiquitin-like proteins and smaller functional groups. Considering different combinations of post-translational modifications can give rise to distinct biological outcomes, characterizing ubiquitylated proteoforms of a given protein is paramount. In this Opinion, we review recent advances in detecting and...
Source: Current Opinion in Chemical Biology - April 4, 2021 Category: Biochemistry Authors: Kirandeep K Deol Eric R Strieter Source Type: research

Computational modeling of carbohydrate processing enzymes reactions
Curr Opin Chem Biol. 2021 Mar 30;61:203-213. doi: 10.1016/j.cbpa.2021.02.012. Online ahead of print.ABSTRACTCarbohydrate processing enzymes are of biocatalytic interest. Glycoside hydrolases and the recently discovered lytic polysaccharide monooxygenase for their use in biomass degradation to obtain biofuels or valued chemical entities. Glycosyltransferases or engineered glycosidases and phosphorylases for the synthesis of carbohydrates and glycosylated products. Quantum mechanics-molecular mechanics (QM/MM) methods are highly contributing to establish their different chemical reaction mechanisms. Other computational metho...
Source: Current Opinion in Chemical Biology - April 3, 2021 Category: Biochemistry Authors: Fernanda Mendoza Laura Masgrau Source Type: research

Intrinsically disordered proteins and biomolecular condensates as drug targets
Curr Opin Chem Biol. 2021 Mar 31;62:90-100. doi: 10.1016/j.cbpa.2021.02.009. Online ahead of print.ABSTRACTIntrinsically disordered domains represent attractive therapeutic targets because they play key roles in cancer, as well as in neurodegenerative and infectious diseases. They are, however, considered undruggable because they do not form stable binding pockets for small molecules and, therefore, have not been prioritized in drug discovery. Under physiological solution conditions many biomedically relevant intrinsically disordered proteins undergo phase separation processes leading to the formation of mesoscopic highly ...
Source: Current Opinion in Chemical Biology - April 3, 2021 Category: Biochemistry Authors: Mateusz Biesaga Marta Frigol é-Vivas Xavier Salvatella Source Type: research

Computational modeling of carbohydrate processing enzymes reactions
Curr Opin Chem Biol. 2021 Mar 30;61:203-213. doi: 10.1016/j.cbpa.2021.02.012. Online ahead of print.ABSTRACTCarbohydrate processing enzymes are of biocatalytic interest. Glycoside hydrolases and the recently discovered lytic polysaccharide monooxygenase for their use in biomass degradation to obtain biofuels or valued chemical entities. Glycosyltransferases or engineered glycosidases and phosphorylases for the synthesis of carbohydrates and glycosylated products. Quantum mechanics-molecular mechanics (QM/MM) methods are highly contributing to establish their different chemical reaction mechanisms. Other computational metho...
Source: Current Opinion in Chemical Biology - April 3, 2021 Category: Biochemistry Authors: Fernanda Mendoza Laura Masgrau Source Type: research

Intrinsically disordered proteins and biomolecular condensates as drug targets
Curr Opin Chem Biol. 2021 Mar 31;62:90-100. doi: 10.1016/j.cbpa.2021.02.009. Online ahead of print.ABSTRACTIntrinsically disordered domains represent attractive therapeutic targets because they play key roles in cancer, as well as in neurodegenerative and infectious diseases. They are, however, considered undruggable because they do not form stable binding pockets for small molecules and, therefore, have not been prioritized in drug discovery. Under physiological solution conditions many biomedically relevant intrinsically disordered proteins undergo phase separation processes leading to the formation of mesoscopic highly ...
Source: Current Opinion in Chemical Biology - April 3, 2021 Category: Biochemistry Authors: Mateusz Biesaga Marta Frigol é-Vivas Xavier Salvatella Source Type: research

Biological activities of polypyridyl-type ligands: implications for bioinorganic chemistry and light-activated metal complexes
Curr Opin Chem Biol. 2021 Mar 30;61:191-202. doi: 10.1016/j.cbpa.2021.01.016. Online ahead of print.ABSTRACTPolypyridyl coordinating ligands are common in metal complexes used in medicinal inorganic chemistry. These ligands possess intrinsic cytotoxicity, but detailed data on this phenomenon are sparse, and cytotoxicity values vary widely and are often irreproducible. To provide new insights into the biological effects of bipyridyl-type ligands and structurally related metal-binding systems, reports of free ligand cytotoxicity were reviewed. The cytotoxicity of 25 derivatives of 2,2'-bipyridine and 1,10-phenanthroline demo...
Source: Current Opinion in Chemical Biology - April 2, 2021 Category: Biochemistry Authors: Austin C Hachey Dmytro Havrylyuk Edith C Glazer Source Type: research

Editorial: Biocatalytic opportunities to harness the structural diversity of carbohydrates
Curr Opin Chem Biol. 2021 Mar 28:S1367-5931(21)00033-8. doi: 10.1016/j.cbpa.2021.02.011. Online ahead of print.NO ABSTRACTPMID:33789809 | DOI:10.1016/j.cbpa.2021.02.011 (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - April 1, 2021 Category: Biochemistry Authors: Bernd Nidetzky Tom Desmet Source Type: research

Editorial: Biocatalytic opportunities to harness the structural diversity of carbohydrates
Curr Opin Chem Biol. 2021 Mar 28:S1367-5931(21)00033-8. doi: 10.1016/j.cbpa.2021.02.011. Online ahead of print.NO ABSTRACTPMID:33789809 | DOI:10.1016/j.cbpa.2021.02.011 (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - April 1, 2021 Category: Biochemistry Authors: Bernd Nidetzky Tom Desmet Source Type: research

Editorial: Biocatalytic opportunities to harness the structural diversity of carbohydrates
Curr Opin Chem Biol. 2021 Mar 28:S1367-5931(21)00033-8. doi: 10.1016/j.cbpa.2021.02.011. Online ahead of print.NO ABSTRACTPMID:33789809 | DOI:10.1016/j.cbpa.2021.02.011 (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - April 1, 2021 Category: Biochemistry Authors: Bernd Nidetzky Tom Desmet Source Type: research

Systems for in  vivo hypermutation: a quest for scale and depth in directed evolution
We describe various in vivo hypermutation systems for continuous evolution, discuss how different architectures for in vivo hypermutation facilitate evolutionary search scale and depth in their application to problems in protein evolution and engineering, and outline future opportunities for the field.PMID:33784581 | DOI:10.1016/j.cbpa.2021.02.008 (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 30, 2021 Category: Biochemistry Authors: Gordon Rix Chang C Liu Source Type: research

Metal complexes as optical probes for DNA sensing and imaging
Curr Opin Chem Biol. 2021 Mar 26;61:179-190. doi: 10.1016/j.cbpa.2021.02.007. Online ahead of print.ABSTRACTTransition and lanthanide metal complexes have rich photophysical properties that can be used for cellular imaging, biosensing and phototherapy. One of the applications of such luminescent compounds is the detection and visualisation of nucleic acids. In this brief review, we survey the recent literature on the use of luminescent metal complexes (including ReI, RuII, OsII, IrIII, PtII, EuIII and TbIII) as DNA optical probes, including examples of compounds that bind selectively to non-duplex DNA topologies such as qu...
Source: Current Opinion in Chemical Biology - March 30, 2021 Category: Biochemistry Authors: Jessica Berrones Reyes Marina K Kuimova Ramon Vilar Source Type: research

Targeting of extracellular protein-protein interactions with macrocyclic peptides
Curr Opin Chem Biol. 2021 Mar 25;62:82-89. doi: 10.1016/j.cbpa.2021.02.013. Online ahead of print.ABSTRACTTargeting of extracellular protein-protein interactions (PPI) is emerging as a major application for de novo discovered macrocyclic peptides. Modern discovery platforms can routinely identify macrocyclic peptide ligands capable of highly selective modulation of extracellular signaling pathways; amenability to chemical synthesis and natural modularity of peptides additionally provides an avenue for their further structural elaboration, while the challenge of cell internalization can be minimized. Here, we discuss the re...
Source: Current Opinion in Chemical Biology - March 28, 2021 Category: Biochemistry Authors: Shota Taguchi Hiroaki Suga Source Type: research

Targeting of extracellular protein-protein interactions with macrocyclic peptides
Curr Opin Chem Biol. 2021 Mar 25;62:82-89. doi: 10.1016/j.cbpa.2021.02.013. Online ahead of print.ABSTRACTTargeting of extracellular protein-protein interactions (PPI) is emerging as a major application for de novo discovered macrocyclic peptides. Modern discovery platforms can routinely identify macrocyclic peptide ligands capable of highly selective modulation of extracellular signaling pathways; amenability to chemical synthesis and natural modularity of peptides additionally provides an avenue for their further structural elaboration, while the challenge of cell internalization can be minimized. Here, we discuss the re...
Source: Current Opinion in Chemical Biology - March 28, 2021 Category: Biochemistry Authors: Shota Taguchi Hiroaki Suga Source Type: research

Targeting of extracellular protein-protein interactions with macrocyclic peptides
Curr Opin Chem Biol. 2021 Mar 25;62:82-89. doi: 10.1016/j.cbpa.2021.02.013. Online ahead of print.ABSTRACTTargeting of extracellular protein-protein interactions (PPI) is emerging as a major application for de novo discovered macrocyclic peptides. Modern discovery platforms can routinely identify macrocyclic peptide ligands capable of highly selective modulation of extracellular signaling pathways; amenability to chemical synthesis and natural modularity of peptides additionally provides an avenue for their further structural elaboration, while the challenge of cell internalization can be minimized. Here, we discuss the re...
Source: Current Opinion in Chemical Biology - March 28, 2021 Category: Biochemistry Authors: Shota Taguchi Hiroaki Suga Source Type: research

Emerging tools for bioluminescence imaging
Curr Opin Chem Biol. 2021 Mar 23;63:86-94. doi: 10.1016/j.cbpa.2021.02.005. Online ahead of print.ABSTRACTBioluminescence (BL) relies on the enzymatic reaction between luciferase, a substrate conventionally named luciferin, and various cofactors. BL imaging has become a widely used technique to interrogate gene expression and cell fate, both in small and large animal models of research. Recent developments include the generation of improved luciferase-luciferin systems for deeper and more sensitive imaging as well as new caged luciferins to report on enzymatic activity and other intracellular functions. Here, we critically...
Source: Current Opinion in Chemical Biology - March 26, 2021 Category: Biochemistry Authors: Giorgia Zambito Chintan Chawda Laura Mezzanotte Source Type: research

Emerging tools for bioluminescence imaging
Curr Opin Chem Biol. 2021 Mar 23;63:86-94. doi: 10.1016/j.cbpa.2021.02.005. Online ahead of print.ABSTRACTBioluminescence (BL) relies on the enzymatic reaction between luciferase, a substrate conventionally named luciferin, and various cofactors. BL imaging has become a widely used technique to interrogate gene expression and cell fate, both in small and large animal models of research. Recent developments include the generation of improved luciferase-luciferin systems for deeper and more sensitive imaging as well as new caged luciferins to report on enzymatic activity and other intracellular functions. Here, we critically...
Source: Current Opinion in Chemical Biology - March 26, 2021 Category: Biochemistry Authors: Giorgia Zambito Chintan Chawda Laura Mezzanotte Source Type: research

Imaging-guided nanomedicine development
Curr Opin Chem Biol. 2021 Mar 15;63:78-85. doi: 10.1016/j.cbpa.2021.01.014. Online ahead of print.ABSTRACTNanomedicine research is an active field that produces thousands of studies every year. However, translation of nanotherapeutics to the clinic has yet to catch up with such a vast output. In recent years, the need to better understand nanomedicines' in vivo behavior has been identified as one of the major challenges for efficient clinical translation. In this context, noninvasive imaging offers attractive solutions to provide valuable information about nanomedicine biodistribution, pharmacokinetics, stability, or thera...
Source: Current Opinion in Chemical Biology - March 18, 2021 Category: Biochemistry Authors: Aurora Bernal Claudia Calcagno Willem J M Mulder Carlos P érez-Medina Source Type: research

Imaging-guided nanomedicine development
Curr Opin Chem Biol. 2021 Mar 15;63:78-85. doi: 10.1016/j.cbpa.2021.01.014. Online ahead of print.ABSTRACTNanomedicine research is an active field that produces thousands of studies every year. However, translation of nanotherapeutics to the clinic has yet to catch up with such a vast output. In recent years, the need to better understand nanomedicines' in vivo behavior has been identified as one of the major challenges for efficient clinical translation. In this context, noninvasive imaging offers attractive solutions to provide valuable information about nanomedicine biodistribution, pharmacokinetics, stability, or thera...
Source: Current Opinion in Chemical Biology - March 18, 2021 Category: Biochemistry Authors: Aurora Bernal Claudia Calcagno Willem J M Mulder Carlos P érez-Medina Source Type: research

Imaging-guided nanomedicine development
Curr Opin Chem Biol. 2021 Mar 15;63:78-85. doi: 10.1016/j.cbpa.2021.01.014. Online ahead of print.ABSTRACTNanomedicine research is an active field that produces thousands of studies every year. However, translation of nanotherapeutics to the clinic has yet to catch up with such a vast output. In recent years, the need to better understand nanomedicines' in vivo behavior has been identified as one of the major challenges for efficient clinical translation. In this context, noninvasive imaging offers attractive solutions to provide valuable information about nanomedicine biodistribution, pharmacokinetics, stability, or thera...
Source: Current Opinion in Chemical Biology - March 18, 2021 Category: Biochemistry Authors: Aurora Bernal Claudia Calcagno Willem J M Mulder Carlos P érez-Medina Source Type: research

Imaging-guided nanomedicine development
Curr Opin Chem Biol. 2021 Mar 15;63:78-85. doi: 10.1016/j.cbpa.2021.01.014. Online ahead of print.ABSTRACTNanomedicine research is an active field that produces thousands of studies every year. However, translation of nanotherapeutics to the clinic has yet to catch up with such a vast output. In recent years, the need to better understand nanomedicines' in vivo behavior has been identified as one of the major challenges for efficient clinical translation. In this context, noninvasive imaging offers attractive solutions to provide valuable information about nanomedicine biodistribution, pharmacokinetics, stability, or thera...
Source: Current Opinion in Chemical Biology - March 18, 2021 Category: Biochemistry Authors: Aurora Bernal Claudia Calcagno Willem J M Mulder Carlos P érez-Medina Source Type: research

Imaging-guided nanomedicine development
Curr Opin Chem Biol. 2021 Mar 15;63:78-85. doi: 10.1016/j.cbpa.2021.01.014. Online ahead of print.ABSTRACTNanomedicine research is an active field that produces thousands of studies every year. However, translation of nanotherapeutics to the clinic has yet to catch up with such a vast output. In recent years, the need to better understand nanomedicines' in vivo behavior has been identified as one of the major challenges for efficient clinical translation. In this context, noninvasive imaging offers attractive solutions to provide valuable information about nanomedicine biodistribution, pharmacokinetics, stability, or thera...
Source: Current Opinion in Chemical Biology - March 18, 2021 Category: Biochemistry Authors: Aurora Bernal Claudia Calcagno Willem J M Mulder Carlos P érez-Medina Source Type: research

Imaging-guided nanomedicine development
Curr Opin Chem Biol. 2021 Mar 15;63:78-85. doi: 10.1016/j.cbpa.2021.01.014. Online ahead of print.ABSTRACTNanomedicine research is an active field that produces thousands of studies every year. However, translation of nanotherapeutics to the clinic has yet to catch up with such a vast output. In recent years, the need to better understand nanomedicines' in vivo behavior has been identified as one of the major challenges for efficient clinical translation. In this context, noninvasive imaging offers attractive solutions to provide valuable information about nanomedicine biodistribution, pharmacokinetics, stability, or thera...
Source: Current Opinion in Chemical Biology - March 18, 2021 Category: Biochemistry Authors: Aurora Bernal Claudia Calcagno Willem J M Mulder Carlos P érez-Medina Source Type: research

Imaging-guided nanomedicine development
Curr Opin Chem Biol. 2021 Mar 15;63:78-85. doi: 10.1016/j.cbpa.2021.01.014. Online ahead of print.ABSTRACTNanomedicine research is an active field that produces thousands of studies every year. However, translation of nanotherapeutics to the clinic has yet to catch up with such a vast output. In recent years, the need to better understand nanomedicines' in vivo behavior has been identified as one of the major challenges for efficient clinical translation. In this context, noninvasive imaging offers attractive solutions to provide valuable information about nanomedicine biodistribution, pharmacokinetics, stability, or thera...
Source: Current Opinion in Chemical Biology - March 18, 2021 Category: Biochemistry Authors: Aurora Bernal Claudia Calcagno Willem J M Mulder Carlos P érez-Medina Source Type: research

Harnessing the power of directed evolution to improve genome editing systems
Curr Opin Chem Biol. 2021 Mar 13;64:10-19. doi: 10.1016/j.cbpa.2021.02.004. Online ahead of print.ABSTRACTThe recent development of genome editing systems, such as zinc-finger nucleases, transcription activator-like effectors, CRISPR-Cas nucleases, and base editors has enabled the unprecedented capability to engineer the genomes of living cells. The ever-increasing demand for genome editors with improved accuracy, activity, and functionality has stimulated significant efforts to further engineer the genome editing systems. Directed evolution represents a promising strategy to improve the existing genome editing systems and...
Source: Current Opinion in Chemical Biology - March 16, 2021 Category: Biochemistry Authors: Qiwen Su Mi Zhou Cristina Cheng Jia Niu Source Type: research

Harnessing the power of directed evolution to improve genome editing systems
Curr Opin Chem Biol. 2021 Mar 13;64:10-19. doi: 10.1016/j.cbpa.2021.02.004. Online ahead of print.ABSTRACTThe recent development of genome editing systems, such as zinc-finger nucleases, transcription activator-like effectors, CRISPR-Cas nucleases, and base editors has enabled the unprecedented capability to engineer the genomes of living cells. The ever-increasing demand for genome editors with improved accuracy, activity, and functionality has stimulated significant efforts to further engineer the genome editing systems. Directed evolution represents a promising strategy to improve the existing genome editing systems and...
Source: Current Opinion in Chemical Biology - March 16, 2021 Category: Biochemistry Authors: Qiwen Su Mi Zhou Cristina Cheng Jia Niu Source Type: research

Inhibition of glutaminolysis in combination with other therapies to improve cancer treatment
Curr Opin Chem Biol. 2021 Mar 12;62:64-81. doi: 10.1016/j.cbpa.2021.01.006. Online ahead of print.ABSTRACTTargeting glutamine catabolism has been attracting more research attention on the development of successful cancer therapy. Catalytic enzymes such as glutaminase (GLS) in glutaminolysis, a series of biochemical reactions by which glutamine is converted to glutamate and then alpha-ketoglutarate, an intermediate of the tricarboxylic acid (TCA) cycle, can be targeted by small molecule inhibitors, some of which are undergoing early phase clinical trials and exhibiting promising safety profiles. However, resistance to gluta...
Source: Current Opinion in Chemical Biology - March 15, 2021 Category: Biochemistry Authors: Yao-An Shen Chi-Long Chen Yi-Hsuan Huang Emily Elizabeth Evans Chun-Chia Cheng Ya-Jie Chuang Cissy Zhang Anne Le Source Type: research

Inhibition of glutaminolysis in combination with other therapies to improve cancer treatment
Curr Opin Chem Biol. 2021 Mar 12;62:64-81. doi: 10.1016/j.cbpa.2021.01.006. Online ahead of print.ABSTRACTTargeting glutamine catabolism has been attracting more research attention on the development of successful cancer therapy. Catalytic enzymes such as glutaminase (GLS) in glutaminolysis, a series of biochemical reactions by which glutamine is converted to glutamate and then alpha-ketoglutarate, an intermediate of the tricarboxylic acid (TCA) cycle, can be targeted by small molecule inhibitors, some of which are undergoing early phase clinical trials and exhibiting promising safety profiles. However, resistance to gluta...
Source: Current Opinion in Chemical Biology - March 15, 2021 Category: Biochemistry Authors: Yao-An Shen Chi-Long Chen Yi-Hsuan Huang Emily Elizabeth Evans Chun-Chia Cheng Ya-Jie Chuang Cissy Zhang Anne Le Source Type: research

Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy
Curr Opin Chem Biol. 2021 Mar 11;61:170-178. doi: 10.1016/j.cbpa.2021.01.015. Online ahead of print.ABSTRACTChemical tools capable of detecting ferrous iron with oxidation-state specificity have only recently become available. Coincident with this development in chemical biology has been increased study and appreciation for the importance of ferrous iron during infection and more generally in host-pathogen interaction. Some of the recent findings are surprising and challenge long-standing assumptions about bacterial iron homeostasis and the innate immune response to infection. Here, we review these recent developments and ...
Source: Current Opinion in Chemical Biology - March 14, 2021 Category: Biochemistry Authors: Ryan L Gonciarz Adam R Renslo Source Type: research

Advancements in chemical biology targeting the kinases and phosphatases of RNA polymerase II-mediated transcription
Curr Opin Chem Biol. 2021 Mar 11;63:68-77. doi: 10.1016/j.cbpa.2021.02.002. Online ahead of print.ABSTRACTPhosphorylation of RNA polymerase II (RNAP II) coordinates the temporal progression of eukaryotic transcription. The development and application of chemical genetic methods have enhanced our ability to investigate the intricate and intertwined pathways regulated by the kinases and phosphatases targeting RNAP II to ensure transcription accuracy and efficiency. Although identifying small molecules that modulate these enzymes has been challenging due to their highly conserved structures, powerful new chemical biology stra...
Source: Current Opinion in Chemical Biology - March 14, 2021 Category: Biochemistry Authors: Wantae Kim Blase LeBlanc Wendy L Matthews Zhong-Yin Zhang Yan Zhang Source Type: research

Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy
Curr Opin Chem Biol. 2021 Mar 11;61:170-178. doi: 10.1016/j.cbpa.2021.01.015. Online ahead of print.ABSTRACTChemical tools capable of detecting ferrous iron with oxidation-state specificity have only recently become available. Coincident with this development in chemical biology has been increased study and appreciation for the importance of ferrous iron during infection and more generally in host-pathogen interaction. Some of the recent findings are surprising and challenge long-standing assumptions about bacterial iron homeostasis and the innate immune response to infection. Here, we review these recent developments and ...
Source: Current Opinion in Chemical Biology - March 14, 2021 Category: Biochemistry Authors: Ryan L Gonciarz Adam R Renslo Source Type: research

Advancements in chemical biology targeting the kinases and phosphatases of RNA polymerase II-mediated transcription
Curr Opin Chem Biol. 2021 Mar 11;63:68-77. doi: 10.1016/j.cbpa.2021.02.002. Online ahead of print.ABSTRACTPhosphorylation of RNA polymerase II (RNAP II) coordinates the temporal progression of eukaryotic transcription. The development and application of chemical genetic methods have enhanced our ability to investigate the intricate and intertwined pathways regulated by the kinases and phosphatases targeting RNAP II to ensure transcription accuracy and efficiency. Although identifying small molecules that modulate these enzymes has been challenging due to their highly conserved structures, powerful new chemical biology stra...
Source: Current Opinion in Chemical Biology - March 14, 2021 Category: Biochemistry Authors: Wantae Kim Blase LeBlanc Wendy L Matthews Zhong-Yin Zhang Yan Zhang Source Type: research

Opportunity knocks for uncovering the new function of an understudied nucleosome remodeling complex member, the bromodomain PHD finger transcription factor, BPTF
Curr Opin Chem Biol. 2021 Mar 8;63:57-67. doi: 10.1016/j.cbpa.2021.02.003. Online ahead of print.ABSTRACTNucleosome remodeling provides access to genomic DNA for recruitment of the transcriptional machinery to mediate gene expression. The aberrant function of nucleosome remodeling complexes has been correlated to human cancer, making them emerging therapeutic targets. The bromodomain PHD finger transcription factor, BPTF, is the largest member of the human nucleosome remodeling factor NURF. Over the last five years, BPTF has become increasingly identified as a protumorigenic factor, prompting investigations into the molecu...
Source: Current Opinion in Chemical Biology - March 11, 2021 Category: Biochemistry Authors: Huda Zahid Noelle M Olson William C K Pomerantz Source Type: research

Metal-based environment-sensitive MRI contrast agents
Curr Opin Chem Biol. 2021 Mar 8;61:154-169. doi: 10.1016/j.cbpa.2021.01.013. Online ahead of print.ABSTRACTInteractions of paramagnetic metal complexes with their biological environment can modulate their magnetic resonance imaging (MRI) contrast-enhancing properties in different ways, and this has been widely exploited to create responsive probes that can provide biochemical information. We survey progress in two rapidly growing areas: the MRI detection of biologically important metal ions, such as calcium, zinc, and copper, and the use of transition metal complexes as smart MRI agents. In both fields, new imaging technol...
Source: Current Opinion in Chemical Biology - March 11, 2021 Category: Biochemistry Authors: C élia S Bonnet Éva Tóth Source Type: research

Opportunity knocks for uncovering the new function of an understudied nucleosome remodeling complex member, the bromodomain PHD finger transcription factor, BPTF
Curr Opin Chem Biol. 2021 Mar 8;63:57-67. doi: 10.1016/j.cbpa.2021.02.003. Online ahead of print.ABSTRACTNucleosome remodeling provides access to genomic DNA for recruitment of the transcriptional machinery to mediate gene expression. The aberrant function of nucleosome remodeling complexes has been correlated to human cancer, making them emerging therapeutic targets. The bromodomain PHD finger transcription factor, BPTF, is the largest member of the human nucleosome remodeling factor NURF. Over the last five years, BPTF has become increasingly identified as a protumorigenic factor, prompting investigations into the molecu...
Source: Current Opinion in Chemical Biology - March 11, 2021 Category: Biochemistry Authors: Huda Zahid Noelle M Olson William C K Pomerantz Source Type: research

Metal-based environment-sensitive MRI contrast agents
Curr Opin Chem Biol. 2021 Mar 8;61:154-169. doi: 10.1016/j.cbpa.2021.01.013. Online ahead of print.ABSTRACTInteractions of paramagnetic metal complexes with their biological environment can modulate their magnetic resonance imaging (MRI) contrast-enhancing properties in different ways, and this has been widely exploited to create responsive probes that can provide biochemical information. We survey progress in two rapidly growing areas: the MRI detection of biologically important metal ions, such as calcium, zinc, and copper, and the use of transition metal complexes as smart MRI agents. In both fields, new imaging technol...
Source: Current Opinion in Chemical Biology - March 11, 2021 Category: Biochemistry Authors: C élia S Bonnet Éva Tóth Source Type: research

Opportunity knocks for uncovering the new function of an understudied nucleosome remodeling complex member, the bromodomain PHD finger transcription factor, BPTF
Curr Opin Chem Biol. 2021 Mar 8;63:57-67. doi: 10.1016/j.cbpa.2021.02.003. Online ahead of print.ABSTRACTNucleosome remodeling provides access to genomic DNA for recruitment of the transcriptional machinery to mediate gene expression. The aberrant function of nucleosome remodeling complexes has been correlated to human cancer, making them emerging therapeutic targets. The bromodomain PHD finger transcription factor, BPTF, is the largest member of the human nucleosome remodeling factor NURF. Over the last five years, BPTF has become increasingly identified as a protumorigenic factor, prompting investigations into the molecu...
Source: Current Opinion in Chemical Biology - March 11, 2021 Category: Biochemistry Authors: Huda Zahid Noelle M Olson William C K Pomerantz Source Type: research

Metal-based environment-sensitive MRI contrast agents
Curr Opin Chem Biol. 2021 Mar 8;61:154-169. doi: 10.1016/j.cbpa.2021.01.013. Online ahead of print.ABSTRACTInteractions of paramagnetic metal complexes with their biological environment can modulate their magnetic resonance imaging (MRI) contrast-enhancing properties in different ways, and this has been widely exploited to create responsive probes that can provide biochemical information. We survey progress in two rapidly growing areas: the MRI detection of biologically important metal ions, such as calcium, zinc, and copper, and the use of transition metal complexes as smart MRI agents. In both fields, new imaging technol...
Source: Current Opinion in Chemical Biology - March 11, 2021 Category: Biochemistry Authors: C élia S Bonnet Éva Tóth Source Type: research

Recent developments in ligands and chemical probes targeting solute carrier transporters
Curr Opin Chem Biol. 2021 Mar 6;62:53-63. doi: 10.1016/j.cbpa.2021.01.012. Online ahead of print.ABSTRACTSolute carrier (SLC) membrane transporters remain a largely unexploited target class, despite their central roles in cell identity and metabolism. This gap is reflected in the lack of high-quality chemical ligands or probes and in the small number of compounds that have progressed toward clinical development. In this review, we discuss recent advancements in SLC ligand discovery as well as new candidates that have been added to the investigational toolkit, with a particular focus on first-in-class ligands and the cognat...
Source: Current Opinion in Chemical Biology - March 10, 2021 Category: Biochemistry Authors: Andrea Casiraghi Ariel Bensimon Giulio Superti-Furga Source Type: research

Chemoenzymatic strategies for RNA modification and labeling
Curr Opin Chem Biol. 2021 Mar 6;63:46-56. doi: 10.1016/j.cbpa.2021.01.008. Online ahead of print.ABSTRACTRNA is a central molecule in numerous cellular processes, including transcription, translation, and regulation of gene expression. To reveal the numerous facets of RNA function and metabolism in cells, labeling has become indispensable and enables the visualization, isolation, characterization, and even quantification of certain RNA species. In this review, we will cover chemoenzymatic approaches for covalent RNA labeling. These approaches rely on an enzymatic step to introduce an RNA modification before conjugation wit...
Source: Current Opinion in Chemical Biology - March 10, 2021 Category: Biochemistry Authors: Johanna Mattay Maria Dittmar Andrea Rentmeister Source Type: research

Recent developments in ligands and chemical probes targeting solute carrier transporters
Curr Opin Chem Biol. 2021 Mar 6;62:53-63. doi: 10.1016/j.cbpa.2021.01.012. Online ahead of print.ABSTRACTSolute carrier (SLC) membrane transporters remain a largely unexploited target class, despite their central roles in cell identity and metabolism. This gap is reflected in the lack of high-quality chemical ligands or probes and in the small number of compounds that have progressed toward clinical development. In this review, we discuss recent advancements in SLC ligand discovery as well as new candidates that have been added to the investigational toolkit, with a particular focus on first-in-class ligands and the cognat...
Source: Current Opinion in Chemical Biology - March 10, 2021 Category: Biochemistry Authors: Andrea Casiraghi Ariel Bensimon Giulio Superti-Furga Source Type: research

Chemoenzymatic strategies for RNA modification and labeling
Curr Opin Chem Biol. 2021 Mar 6;63:46-56. doi: 10.1016/j.cbpa.2021.01.008. Online ahead of print.ABSTRACTRNA is a central molecule in numerous cellular processes, including transcription, translation, and regulation of gene expression. To reveal the numerous facets of RNA function and metabolism in cells, labeling has become indispensable and enables the visualization, isolation, characterization, and even quantification of certain RNA species. In this review, we will cover chemoenzymatic approaches for covalent RNA labeling. These approaches rely on an enzymatic step to introduce an RNA modification before conjugation wit...
Source: Current Opinion in Chemical Biology - March 10, 2021 Category: Biochemistry Authors: Johanna Mattay Maria Dittmar Andrea Rentmeister Source Type: research

Cytokine engineering for targeted cancer immunotherapy
Curr Opin Chem Biol. 2021 Mar 5;62:43-52. doi: 10.1016/j.cbpa.2021.01.007. Online ahead of print.ABSTRACTCytokines are key modulators of the immune responses and represent promising therapeutics for a variety of cancers. However, successful translation of cytokine-based therapy to the clinic is limited by, among others, severe toxicities and lack of efficacy due to cytokine pleiotropy and off-target activation of cells. Engineering cytokines with enhanced therapeutic properties has emerged as a promising strategy to overcome these challenges. Advances in protein engineering and protein-polymer conjugate technologies have f...
Source: Current Opinion in Chemical Biology - March 8, 2021 Category: Biochemistry Authors: Lucia Bonati Li Tang Source Type: research

Mapping messenger RNA methylations at single base resolution
Curr Opin Chem Biol. 2021 Mar 5;63:28-37. doi: 10.1016/j.cbpa.2021.02.001. Online ahead of print.ABSTRACTThe messenger RNA (mRNA) methylations in mammalian cells have been found to contain N6-methyladenosine (m6A), N6-2'-O-dimethyladenosine (m6Am), 7-methylguanosine (m7G), 1-methyladenosine (m1A), 5-methylcytosine (m5C), and 2'-O-methylation (2'-OMe). Their regulatory functions in control of mRNA fate and gene expression are being increasingly uncovered. To unambiguously understand the critical roles of mRNA methylations in physiological and pathological processes, mapping these methylations at single base resolution is hi...
Source: Current Opinion in Chemical Biology - March 8, 2021 Category: Biochemistry Authors: Jie Cao Xiao Shu Xin-Hua Feng Jianzhao Liu Source Type: research

Not so innocent: Impact of fluorophore chemistry on the in  vivo properties of bioconjugates
Curr Opin Chem Biol. 2021 Mar 5;63:38-45. doi: 10.1016/j.cbpa.2021.01.009. Online ahead of print.ABSTRACTThe combination of targeting ligands and fluorescent dyes is a powerful strategy to observe cell types and tissues of interest. Conjugates of peptides, proteins, and, in particular, monoclonal antibodies (mAbs) exhibit excellent tumor targeting in various contexts. This approach has been translated to a clinical setting to provide real-time molecular insights during the surgical resection of solid tumors. A critical element of this approach is the generation of highly fluorescent bioconjugates that maintain the properti...
Source: Current Opinion in Chemical Biology - March 8, 2021 Category: Biochemistry Authors: Syed Muhammad Usama Ek Raj Thapaliya Michael P Luciano Martin J Schnermann Source Type: research