Effect of Sulfotyrosine and Negatively Charged Amino Acid of Leech-Derived Peptides on Binding and Inhibitory Activity Against Thrombin
Chembiochem. 2023 Dec 6:e202300744. doi: 10.1002/cbic.202300744. Online ahead of print.ABSTRACTHirudins, natural sulfo(glyco)proteins, are clinical anticoagulants that directly inhibit thrombin, a key coagulation factor. Their potent thrombin inhibition primarily results from antagonistic interactions with both the catalytic and non-catalytic sites of thrombin. Hirudins often feature sulfate moieties on Tyr residues in their anionic C-terminus region, enabling strong interactions with thrombin exosite-I and effectively blocking its engagement with fibrinogen. Although sulfotyrosines have been identified in various hirudin ...
Source: Chembiochem - December 6, 2023 Category: Biochemistry Authors: Tzu-Yin Chen Eileen Shyur Tzu-Hsuan Ma Lakshmi Wijeyewickrema Sheng-Wei Lin Mu-Rong Kao Pi-Hui Liang Jiun-Jie Shie Er-Yuan Chuang Jing-Ping Liou Yves Sy Hsieh Source Type: research
Discovery and Development of Cyclic Peptide Proteasome Stimulators
Chembiochem. 2023 Dec 6:e202300671. doi: 10.1002/cbic.202300671. Online ahead of print.ABSTRACTThe proteasome degrades proteins, which is essential for cellular homeostasis. Ubiquitin independent proteolysis degrades highly disordered and misfolded proteins. A decline of proteasomal activity has been associated with multiple neurodegenerative diseases due to the accumulation of misfolded proteins. In this work, cyclic peptide proteasome stimulators (CyPPSs) that enhance the clearance of misfolded proteins were discovered. In the initial screen of predicted natural products (pNPs), several cyclic peptides were found to stim...
Source: Chembiochem - December 6, 2023 Category: Biochemistry Authors: Samantha Nelson Timothy J Harris Christine S Muli Marianne E Maresch Braden Baker Chloe Smith Chris Neumann Darci J Trader Elizabeth I Parkinson Source Type: research
Two-Factor Fluorogenic Cyanine-Styryl Dyes with Yellow and Red Fluorescence for Bioorthogonal Labelling of DNA
Chembiochem. 2023 Dec 5:e202300739. doi: 10.1002/cbic.202300739. Online ahead of print.ABSTRACTAn orange- and a red-emitting tetrazine-modified cyanine-styryl dyes were synthesized for bioorthogonal labelling of DNA by means of the Diels-Alder reaction with inverse electron demand. Both dyes use the concept of the "two-factor" fluorogenicity for nucleic acids: (i) The dyes are nucleic-acid sensitive by their non-covalent binding to DNA, and (ii) their covalently attached tetrazine moiety quench the fluorescence. As a result, the reaction with bicyclononyne- and spirohexene-modified DNA is significantly accelerated up to k2...
Source: Chembiochem - December 5, 2023 Category: Biochemistry Authors: Bastian Pfeuffer Philipp Geng Hans-Achim Wagenknecht Source Type: research
Enzymatic Strategies for the Biosynthesis of N-Acyl Amino Acid Amides
Chembiochem. 2023 Dec 5:e202300672. doi: 10.1002/cbic.202300672. Online ahead of print.ABSTRACTAmide bond-containing biomolecules are functionally significant and useful compounds with diverse applications. For example, N-acyl amino acids (NAAAs) are an important class of lipoamino acid amides with extensive use in food, cosmetic and pharmaceutical industries. Their conventional chemical synthesis involves the use of toxic chlorinating agents for carboxylic acid activation. Enzyme-catalyzed biotransformation for the green synthesis of these amides is therefore highly desirable. Here, we review a range of enzymes suitable f...
Source: Chembiochem - December 5, 2023 Category: Biochemistry Authors: Glen Kai Bin Kua Giang Kien Truc Nguyen Zhi Li Source Type: research
High-Density Immobilization of TCEP on Silica Beads for Efficient Disulfide Reduction and Thiol Alkylation in Peptides
Chembiochem. 2023 Dec 4:e202300592. doi: 10.1002/cbic.202300592. Online ahead of print.ABSTRACTTris-(2-carboxyethyl)phosphine (TCEP) linked to agarose beads is widely used for reducing disulfide bridges in proteins and peptides. The immobilization of TCEP on beads allows efficient removal after reduction to prevent its reaction with alkylating reagents and thus interference with conjugation reactions. However, a limitation of agarose TCEP is its relatively low reduction capacity per milliliter of wet beads (about 15 μmol/ml), making it unsuitable for the reduction of disulfides from molecules at millimolar concentrations....
Source: Chembiochem - December 4, 2023 Category: Biochemistry Authors: Mischa Sch üttel Christian Heinis Source Type: research
High-Density Immobilization of TCEP on Silica Beads for Efficient Disulfide Reduction and Thiol Alkylation in Peptides
Chembiochem. 2023 Dec 4:e202300592. doi: 10.1002/cbic.202300592. Online ahead of print.ABSTRACTTris-(2-carboxyethyl)phosphine (TCEP) linked to agarose beads is widely used for reducing disulfide bridges in proteins and peptides. The immobilization of TCEP on beads allows efficient removal after reduction to prevent its reaction with alkylating reagents and thus interference with conjugation reactions. However, a limitation of agarose TCEP is its relatively low reduction capacity per milliliter of wet beads (about 15 μmol/ml), making it unsuitable for the reduction of disulfides from molecules at millimolar concentrations....
Source: Chembiochem - December 4, 2023 Category: Biochemistry Authors: Mischa Sch üttel Christian Heinis Source Type: research
Development and Validation of a Fluorogenic Probe for Lysosomal Zinc Release
Chembiochem. 2023 Dec 1:e202300783. doi: 10.1002/cbic.202300783. Online ahead of print.ABSTRACTZinc homeostasis, which allows optimal zinc utilization in diverse life processes, is responsible for the general well-being of human beings. This paper describes developing and validating an easily accessible indole-containing zinc-specific probe in the cellular milieu. The probe was synthesized from readily available starting materials and was subjected to steady-state fluorescence studies. It showed selective sensing behavior towards Zn2+ with reversible binding. The suppression of PET (Photoinduced Electron Transfer) and ESIP...
Source: Chembiochem - December 1, 2023 Category: Biochemistry Authors: Adarash Kumar Shukla Ashutosh Mahale Savita Choudhary Pravesh Sharma Onkar Prakash Kulkarni Anupam Bhattacharya Source Type: research
Development and Validation of a Fluorogenic Probe for Lysosomal Zinc Release
Chembiochem. 2023 Dec 1:e202300783. doi: 10.1002/cbic.202300783. Online ahead of print.ABSTRACTZinc homeostasis, which allows optimal zinc utilization in diverse life processes, is responsible for the general well-being of human beings. This paper describes developing and validating an easily accessible indole-containing zinc-specific probe in the cellular milieu. The probe was synthesized from readily available starting materials and was subjected to steady-state fluorescence studies. It showed selective sensing behavior towards Zn2+ with reversible binding. The suppression of PET (Photoinduced Electron Transfer) and ESIP...
Source: Chembiochem - December 1, 2023 Category: Biochemistry Authors: Adarash Kumar Shukla Ashutosh Mahale Savita Choudhary Pravesh Sharma Onkar Prakash Kulkarni Anupam Bhattacharya Source Type: research
Development and Validation of a Fluorogenic Probe for Lysosomal Zinc Release
Chembiochem. 2023 Dec 1:e202300783. doi: 10.1002/cbic.202300783. Online ahead of print.ABSTRACTZinc homeostasis, which allows optimal zinc utilization in diverse life processes, is responsible for the general well-being of human beings. This paper describes developing and validating an easily accessible indole-containing zinc-specific probe in the cellular milieu. The probe was synthesized from readily available starting materials and was subjected to steady-state fluorescence studies. It showed selective sensing behavior towards Zn2+ with reversible binding. The suppression of PET (Photoinduced Electron Transfer) and ESIP...
Source: Chembiochem - December 1, 2023 Category: Biochemistry Authors: Adarash Kumar Shukla Ashutosh Mahale Savita Choudhary Pravesh Sharma Onkar Prakash Kulkarni Anupam Bhattacharya Source Type: research
Exploiting the Photo-Physical Properties of Metal Halide Perovskite Nanocrystals for Bioimaging
Chembiochem. 2023 Nov 29:e202300683. doi: 10.1002/cbic.202300683. Online ahead of print.ABSTRACTPerovskite nanomaterials have recently been exploited for bioimaging applications due to their unique photo-physical properties, including high absorbance, good photostability, narrow emissions, and nonlinear optical properties. These attributes outperform conventional fluorescent materials such as organic dyes and metal chalcogenide quantum dots and endow them with the potential to reshape a wide array of bioimaging modalities. Yet, their full potential necessitates a deep grasp of their structure-attribute relationship and str...
Source: Chembiochem - November 30, 2023 Category: Biochemistry Authors: Jiahui Zhang Yifan Zhu Source Type: research
De novo Semi-synthetic Platform for Monitoring Protein degradation in Live Cells
Chembiochem. 2023 Nov 30:e202300731. doi: 10.1002/cbic.202300731. Online ahead of print.ABSTRACTWe designed a platform for monitoring the degradation of exogenous proteins in live cells. We engineered a semi-synthetic platform, which consists of Enhanced Green Fluorescent Protein tagged with SpyCatcher to enable its conjugation to a SpyTag peptide bearing a Von Hippel-Lindau E3 ligand, which was delivered to live cells to promote its degradation. This platform lays the ground for studying the degradation of endogenous proteins equipped with SpyTag and for tracking the degradation of post-translationally modified proteins i...
Source: Chembiochem - November 30, 2023 Category: Biochemistry Authors: Mahdi Hasan Deepanjan Panda Guy Mann Ashraf Brik Source Type: research
Exploiting the Photo-Physical Properties of Metal Halide Perovskite Nanocrystals for Bioimaging
Chembiochem. 2023 Nov 29:e202300683. doi: 10.1002/cbic.202300683. Online ahead of print.ABSTRACTPerovskite nanomaterials have recently been exploited for bioimaging applications due to their unique photo-physical properties, including high absorbance, good photostability, narrow emissions, and nonlinear optical properties. These attributes outperform conventional fluorescent materials such as organic dyes and metal chalcogenide quantum dots and endow them with the potential to reshape a wide array of bioimaging modalities. Yet, their full potential necessitates a deep grasp of their structure-attribute relationship and str...
Source: Chembiochem - November 30, 2023 Category: Biochemistry Authors: Jiahui Zhang Yifan Zhu Source Type: research
De novo Semi-synthetic Platform for Monitoring Protein degradation in Live Cells
Chembiochem. 2023 Nov 30:e202300731. doi: 10.1002/cbic.202300731. Online ahead of print.ABSTRACTWe designed a platform for monitoring the degradation of exogenous proteins in live cells. We engineered a semi-synthetic platform, which consists of Enhanced Green Fluorescent Protein tagged with SpyCatcher to enable its conjugation to a SpyTag peptide bearing a Von Hippel-Lindau E3 ligand, which was delivered to live cells to promote its degradation. This platform lays the ground for studying the degradation of endogenous proteins equipped with SpyTag and for tracking the degradation of post-translationally modified proteins i...
Source: Chembiochem - November 30, 2023 Category: Biochemistry Authors: Mahdi Hasan Deepanjan Panda Guy Mann Ashraf Brik Source Type: research
Data-Driven Protein Engineering for Improving Catalytic Activity and Selectivity
Chembiochem. 2023 Nov 29:e202300754. doi: 10.1002/cbic.202300754. Online ahead of print.ABSTRACTProtein engineering is essential for altering the substrate scope, catalytic activity and selectivity of enzymes for applications in biocatalysis. However, traditional approaches, such as directed evolution and rational design, encounter the challenge in dealing with the experimental screening process of a large protein mutation space. Machine learning methods allow the approximation of protein fitness landscapes and the identification of catalytic patterns using limited experimental data, thus providing a new avenue to guide pr...
Source: Chembiochem - November 29, 2023 Category: Biochemistry Authors: Yu-Fei Ao Mark D örr Marian J Menke Stefan Born Egon Heuson Uwe Bornscheuer Source Type: research
Regulating the Heme Active Site by Covalent Modifications: Two Case Studies of Myoglobin
Chembiochem. 2023 Nov 28:e202300678. doi: 10.1002/cbic.202300678. Online ahead of print.ABSTRACTUsing myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H-1,2,4-triazole-3-thiol and 1-(4-hydroxyphenyl)-1H-pyrrole-2,5-dione. The engineered proteins, termed F46C-triazole Mb and F46C-phenol Mb, respectively, were characterized by X-ray crystallography, spectroscopic and stopped-flow kinetic studies. The results sh...
Source: Chembiochem - November 28, 2023 Category: Biochemistry Authors: Ze-Yuan Chen Hong Yuan Huamin Wang Li-Juan Sun Lu Yu Shu-Qin Gao Xiangshi Tan Ying-Wu Lin Source Type: research
