Tridegin is a potent and specific 66mer peptide inhibitor of coagulation factor XIIIa with six cysteines involved in three disulfide bonds. Three of the 15 possible 3-disulfide-bonded isomers have been identified, which share a bridge between cysteines 19 and 25. We synthesized the three possible 2-disulfide-bonded analogues using a targeted protecting group strategy to investigate the impact of the C-C bond on tridegin's folding, stability, and function. The FXIIIa inhibitory activity of the analogues was retained, which was shown by in vitro fluorogenic activity and whole blood clotting assays. Molecular dynamics simulations of wild-type tridegin and the analogues as well as molecular docking studies with FXIIIa were performed to elucidate the impact of the C-C bond on conformational stability and binding mode. The strategy of selectively reducing disulfide bonds to facilitate large-scale synthesis, while retaining the functionality of disulfide-bonded peptides, has been demonstrated with our present study.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650289 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.8b01982 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single Disulfide Bond in Host Defense Thanatin Analog Peptides: Antimicrobial Activity, Atomic-Resolution Structures and Target Interactions.
Int J Mol Sci
December 2024
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Host defense antimicrobial peptides (AMPs) are promising lead molecules with which to develop antibiotics against drug-resistant bacterial pathogens. Thanatin, an inducible antimicrobial peptide involved in the host defense of insects, is gaining considerable attention in the generation of novel classes of antibiotics. Thanatin or thanatin-based analog peptides are extremely potent in killing bacterial pathogens in the Enterobacteriaceae family, including drug-resistant strains of and .
View Article and Find Full Text PDFInteraction Mechanisms of Cold Atmospheric Plasmas with HIV Capsid Protein by Reactive Molecular Dynamics Simulation.
Molecules
December 2024
School of Electrical Engineering, Shandong University, Jinan 250061, China.
In recent years, plasma medicine has developed rapidly as a new interdisciplinary discipline. However, the key mechanisms of interactions between cold atmospheric plasma (CAP) and biological tissue are still in the exploration stage. In this study, by introducing the reactive molecular dynamics (MD) simulation, the capsid protein (CA) molecule of HIV was selected as the model to investigate the reaction process upon impact by reactive oxygen species (ROS) from CAP and protein molecules at the atomic level.
View Article and Find Full Text PDFRedox modification of mA demethylase SlALKBH2 in tomato regulates fruit ripening.
Nat Plants
January 2025
State Key Laboratory of Plant Diversity and Specialty Crops, Institute of Botany, Chinese Academy of Sciences, Beijing, China.
Hydrogen peroxide (HO) functions as a critical signalling molecule in controlling multiple biological processes. How HO signalling integrates with other regulatory pathways such as epigenetic modification to coordinately regulate plant development remains elusive. Here we report that SlALKBH2, an mA demethylase required for normal ripening of tomato fruit, is sensitive to oxidative modification by HO, which leads to the formation of homodimers mediated by intermolecular disulfide bonds, and Cys39 serves as a key site in this process.
View Article and Find Full Text PDFBiochemical characterization and molecular docking of a novel alkaline-stable keratinase from Amycolatopsis sp. BJA-103.
Int J Biol Macromol
January 2025
College of Life Science, Northwest A&F University, Yangling 712100, China. Electronic address:
Amycolatopsis sp. BJA-103 was isolated for its exceptional feather-degradation capability, leading to the purification, cloning, and heterologous expression of the keratinase enzyme, KER0199. Sequence analysis places KER0199 within the S8 protease family, revealing <60 % sequence similarity to known proteases.
View Article and Find Full Text PDFMagnetic relaxation switch biosensor for detection of Vibrio parahaemolyticus based on photocleavable hydrogel.
Anal Chim Acta
January 2025
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, 315211, PR China. Electronic address:
Background: Foodborne pathogens, particularly Vibrio parahaemolyticus (VP) found in seafood, pose significant health risks, including abdominal pain, nausea, and even death. Rapid, accurate, and sensitive detection of these pathogens is crucial for food safety and public health. However, existing detection methods often require complex sample pretreatment, which limits their practical application.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!