In Silico Study of the Early Stages of Aggregation of β Sheet-forming Antimicrobial Peptide GL13K
Chembiochem. 2024 Apr 4:e202400088. doi: 10.1002/cbic.202400088. Online ahead of print.ABSTRACTAntimicrobial peptides (AMPs) are of growing interest as potential candidates that may offer more resilience against antimicrobial resistance than traditional antibiotic agents. In this article, we perform the first in silico study of the synthetic ß sheet-forming AMP GL13K. Through atomistic simulations of single and multi-peptide systems under different conditions, we are able to shine a light on the short timescales of early aggregation. We find that isolated peptide conformations are primarily dictated by sequence rather tha...
Source: Chembiochem - April 4, 2024 Category: Biochemistry Authors: Mohammadreza Niknam Hamidabad Natalya A Watson Lindsay N Wright Rachael Alexandra Mansbach Source Type: research

Cobalamins function as allosteric activators of an Angelman syndrome-associated UBE3A/E6AP variant
Chembiochem. 2024 Apr 4:e202400184. doi: 10.1002/cbic.202400184. Online ahead of print.ABSTRACTGenetic aberrations of the maternal UBE3A allele, which encodes the E3 ubiquitin ligase E6AP, are the cause of Angelman syndrome (AS), an imprinting disorder. In most cases, the maternal UBE3A allele is not expressed. Yet, approximately 10 percent of AS individuals harbor distinct point mutations in the maternal allele resulting in the expression of full-length E6AP variants that frequently display compromised ligase activity. In a high-throughput screen, we identified cyanocobalamin, a vitamin B12-derivative, and several alloxaz...
Source: Chembiochem - April 4, 2024 Category: Biochemistry Authors: Franziska M üller Jasmin Jansen Fabian Offensperger Daniela Eichbichler Florian Stengel Martin Scheffner Source Type: research

In-vitro Clinical Diagnostics using RNA-Cleaving DNAzymes
Chembiochem. 2024 Apr 4:e202400085. doi: 10.1002/cbic.202400085. Online ahead of print.ABSTRACTOver the last three decades, significant advancements have been made in the development of biosensors and bioassays that use RNA-cleaving DNAzymes (RCDs) as molecular recognition elements. While early examples of RCDs were primarily responsive to metal ions, the past decade has seen numerous RCDs reported for more clinically relevant targets such as bacteria, cancer cells, small metabolites, and protein biomarkers. Over the past 5 years several RCD-based biosensors have also been evaluated using either spiked biological matrixes ...
Source: Chembiochem - April 4, 2024 Category: Biochemistry Authors: Monsur Ali Parameswaran Nair Alfredo Capretta John David Brennan Source Type: research

In Silico Study of the Early Stages of Aggregation of β Sheet-forming Antimicrobial Peptide GL13K
Chembiochem. 2024 Apr 4:e202400088. doi: 10.1002/cbic.202400088. Online ahead of print.ABSTRACTAntimicrobial peptides (AMPs) are of growing interest as potential candidates that may offer more resilience against antimicrobial resistance than traditional antibiotic agents. In this article, we perform the first in silico study of the synthetic ß sheet-forming AMP GL13K. Through atomistic simulations of single and multi-peptide systems under different conditions, we are able to shine a light on the short timescales of early aggregation. We find that isolated peptide conformations are primarily dictated by sequence rather tha...
Source: Chembiochem - April 4, 2024 Category: Biochemistry Authors: Mohammadreza Niknam Hamidabad Natalya A Watson Lindsay N Wright Rachael Alexandra Mansbach Source Type: research

Cobalamins function as allosteric activators of an Angelman syndrome-associated UBE3A/E6AP variant
Chembiochem. 2024 Apr 4:e202400184. doi: 10.1002/cbic.202400184. Online ahead of print.ABSTRACTGenetic aberrations of the maternal UBE3A allele, which encodes the E3 ubiquitin ligase E6AP, are the cause of Angelman syndrome (AS), an imprinting disorder. In most cases, the maternal UBE3A allele is not expressed. Yet, approximately 10 percent of AS individuals harbor distinct point mutations in the maternal allele resulting in the expression of full-length E6AP variants that frequently display compromised ligase activity. In a high-throughput screen, we identified cyanocobalamin, a vitamin B12-derivative, and several alloxaz...
Source: Chembiochem - April 4, 2024 Category: Biochemistry Authors: Franziska M üller Jasmin Jansen Fabian Offensperger Daniela Eichbichler Florian Stengel Martin Scheffner Source Type: research

Molecular Basis for Chemoselectivity Control in Oxidations of Internal Aryl-Alkenes Catalyzed by Laboratory Evolved P450s
Chembiochem. 2024 Apr 3:e202400066. doi: 10.1002/cbic.202400066. Online ahead of print.ABSTRACTP450 enzymes naturally perform selective oxidations of unfunctionalized hydrocarbon substrates, among other reactions. The adaptation of P450 enzymes to particular oxidative reactions involving alkenes is of great interest for the design of new biocatalysts. However, the mechanism that these enzymes utilize to precisely modulate the chemoselectivity and distinguishing between competing alkene double bond epoxidations and allylic C-H hydroxylations is sometimes not clear, which hampers the rational design of specific biocatalysts....
Source: Chembiochem - April 3, 2024 Category: Biochemistry Authors: Jordi Soler Sebastian Gergel Stephan C Hammer Marc Garcia-Borr às Source Type: research

Using Capillary Electrophoresis to Investigate Protein Conformational and Compositional Heterogeneity
Chembiochem. 2024 Apr 3:e202400108. doi: 10.1002/cbic.202400108. Online ahead of print.ABSTRACTDetailed insights into protein structure/function relationships require robust characterization methodologies. Free-solution capillary electrophoresis (CE) is a unique separation technique which is sensitive to the conformation and/or composition of proteins, and therefore provides information on the heterogeneity of these properties. Three unrelated, conformationally/compositionally-altered proteins were separated by CE. An electrophoretic mobility distribution was determined for each protein along with its conformational and/or...
Source: Chembiochem - April 3, 2024 Category: Biochemistry Authors: Aidan B Grosas Mar-Dean Du Plessis Joel J Thevarajah Marianne Gaborieau John Carver Patrice Castignolles Source Type: research

Biological demands and toxicity of isoprenoid precursors in Bacillus subtilis through cell-permeant analogs of isopentenyl pyrophosphate and dimethylallyl pyrophosphate
Chembiochem. 2024 Apr 3:e202400064. doi: 10.1002/cbic.202400064. Online ahead of print.ABSTRACTBacterial isoprenoids are necessary for many biological processes, including maintaining membrane integrity, facilitating intercellular communication, and preventing oxidative damage. All bacterial isoprenoids are biosynthesized from two five carbon structural isomers, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are cell impermeant. Herein, we demonstrate exogenous delivery of IPP and DMAPP into Bacillus subtilis by utilizing a self immolative ester (SIE)-caging approach. We initially evaluated ...
Source: Chembiochem - April 3, 2024 Category: Biochemistry Authors: Dillon McBee Zackary N Hulsey Makayla R Hedges Joshua Baccile Source Type: research

Bile salt hydrolase activity-based probes for monitoring gut microbial bile acid metabolism
Chembiochem. 2024 Apr 2:e202300821. doi: 10.1002/cbic.202300821. Online ahead of print.ABSTRACTBile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are ne...
Source: Chembiochem - April 2, 2024 Category: Biochemistry Authors: Lin Han Raymond Xu Amanda Conwell Sola Takahashi Bibudha Parasar Pamela Chang Source Type: research

Bile salt hydrolase activity-based probes for monitoring gut microbial bile acid metabolism
Chembiochem. 2024 Apr 2:e202300821. doi: 10.1002/cbic.202300821. Online ahead of print.ABSTRACTBile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are ne...
Source: Chembiochem - April 2, 2024 Category: Biochemistry Authors: Lin Han Raymond Xu Amanda Conwell Sola Takahashi Bibudha Parasar Pamela Chang Source Type: research

Halo-1,2,3-triazole: valuable compounds to access biologically relevant molecules
Chembiochem. 2024 Mar 30:e202400150. doi: 10.1002/cbic.202400150. Online ahead of print.ABSTRACT1,2,3-triazole is an important building block in organic chemistry. It is also now well known as bioisostere for various functions, such as the amide or the ester bond, positioning it as key pharmacophore in medicinal chemistry and it has found applications in various fields including life sciences. Attention was first focused on the synthesis of 1,4-disubstituted 1,2,3-triazole molecules but 1,4,5-trisubstituted 1,2,3-triazoles have emerged as valuable molecules due to the possibility to expand the structural modularity. In the...
Source: Chembiochem - March 30, 2024 Category: Biochemistry Authors: Dylan Coelho Yoann Colas M élanie Etheve-Quelquejeu Emmanuelle Braud Laura Iannazzo Source Type: research

Halo-1,2,3-triazole: valuable compounds to access biologically relevant molecules
Chembiochem. 2024 Mar 30:e202400150. doi: 10.1002/cbic.202400150. Online ahead of print.ABSTRACT1,2,3-triazole is an important building block in organic chemistry. It is also now well known as bioisostere for various functions, such as the amide or the ester bond, positioning it as key pharmacophore in medicinal chemistry and it has found applications in various fields including life sciences. Attention was first focused on the synthesis of 1,4-disubstituted 1,2,3-triazole molecules but 1,4,5-trisubstituted 1,2,3-triazoles have emerged as valuable molecules due to the possibility to expand the structural modularity. In the...
Source: Chembiochem - March 30, 2024 Category: Biochemistry Authors: Dylan Coelho Yoann Colas M élanie Etheve-Quelquejeu Emmanuelle Braud Laura Iannazzo Source Type: research

Halo-1,2,3-triazole: valuable compounds to access biologically relevant molecules
Chembiochem. 2024 Mar 30:e202400150. doi: 10.1002/cbic.202400150. Online ahead of print.ABSTRACT1,2,3-triazole is an important building block in organic chemistry. It is also now well known as bioisostere for various functions, such as the amide or the ester bond, positioning it as key pharmacophore in medicinal chemistry and it has found applications in various fields including life sciences. Attention was first focused on the synthesis of 1,4-disubstituted 1,2,3-triazole molecules but 1,4,5-trisubstituted 1,2,3-triazoles have emerged as valuable molecules due to the possibility to expand the structural modularity. In the...
Source: Chembiochem - March 30, 2024 Category: Biochemistry Authors: Dylan Coelho Yoann Colas M élanie Etheve-Quelquejeu Emmanuelle Braud Laura Iannazzo Source Type: research

Peptide-conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications
Chembiochem. 2024 Mar 29:e202300867. doi: 10.1002/cbic.202300867. Online ahead of print.ABSTRACTPeptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, a...
Source: Chembiochem - March 29, 2024 Category: Biochemistry Authors: Bogdan Drago ș Ilieș Ibrahim Yildiz Manzar Abbas Source Type: research

Peptide-conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications
Chembiochem. 2024 Mar 29:e202300867. doi: 10.1002/cbic.202300867. Online ahead of print.ABSTRACTPeptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, a...
Source: Chembiochem - March 29, 2024 Category: Biochemistry Authors: Bogdan Drago ș Ilieș Ibrahim Yildiz Manzar Abbas Source Type: research