AI Article Synopsis
- Researchers successfully created a helical trimer that covers most of the HR1 region of HIV gp41 by chemically linking three identical 51 amino acid peptides.
- They utilized a special pinwheel 'cap' to facilitate the trimerization process through unique chemical properties and protections.
- The resulting protein is fully helical, demonstrating high stability and solubility, making it potentially useful for further studies or applications.
Article Abstract
A helical, prehairpin trimer covering the majority of the HR1 region of human immunodeficiency virus gp41 was achieved by chemically coupling three identical 51 amino acid peptides. A 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene pinwheel 'cap' was used to trimerize the peptides by taking advantage of the unique property of triacyl fluoride and orthogonal protection and deprotection. The resulting protein is fully helical, highly thermostable and soluble.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/psc.1262 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein.
Proc Natl Acad Sci U S A
October 2022
HHMI, Stanford University, Stanford, CA 94305.
Article Synopsis
- * Researchers focused on targeting the viral entry process, specifically a crucial step called membrane fusion, using peptide inhibitors that disrupt the SARS-CoV-2 spike protein's structure.
- * A newly designed peptide showed impressive effectiveness in inhibiting SARS-CoV-2 and its variants, being 100 times more potent than prior versions and suggesting new avenues for developing antiviral treatments.
Article Synopsis
- Variants of SARS-CoV-2 are challenging the effectiveness of current COVID-19 vaccines and treatments, highlighting the need for alternative antivirals that can target less mutated viral processes, such as membrane fusion during viral entry.
- Researchers discovered an extended HR2 peptide that significantly inhibits SARS-CoV-2 infection in various assays, demonstrating stronger performance compared to previous short peptides and maintaining effectiveness against major variants.
- The findings suggest that targeting specific regions outside the conventional HR2 area could lead to the development of more potent peptide-based therapeutics for SARS-CoV-2 and potentially other related viruses.
Concentration-Dependent Structural Transition of the HIV-1 gp41 MPER Peptide into α-Helical Trimers.
Angew Chem Int Ed Engl
January 2021
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA.
The membrane proximal external region (MPER) of HIV-1 gp41 contains epitopes for at least four broadly neutralizing antibodies. Depending on solution conditions and construct design, different structures have been reported for this segment. We show that in aqueous solution the MPER fragment (gp160 ) exists in a monomer-trimer equilibrium with an association constant in the micromolar range.
View Article and Find Full Text PDFRefolding Dynamics of gp41 from Pre-fusion to Pre-hairpin States during HIV-1 Entry.
J Chem Inf Model
January 2020
Key Laboratory of System Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine , Shanghai Jiao Tong University, 800 Dongchuan Road , Shanghai 200240 , China.
The HIV-1 infection is triggered by the binding of the viral envelope glycoprotein (Env) gp120-gp41 trimer to host-cell receptor CD4 and co-receptor CCR5/CXCR4, which leads to substantial conformational changes of Env, that is, structural transition of gp120 from a closed to an open state followed by gp41 refolding from pre-fusion to post-fusion states. The latter finally promotes membrane fusion, likely via visiting a critical pre-hairpin state of gp41. The complete conformational dynamics of the pre-hairpin formation at atomic resolution, however, is still unknown.
View Article and Find Full Text PDFEnfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition.
J Virol
September 2017
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China
The peptide drug enfuvirtide (T20) is the only viral fusion inhibitor used in combination therapy for HIV-1 infection, but it has relatively low antiviral activity and easily induces drug resistance. Emerging studies demonstrate that lipopeptide-based fusion inhibitors, such as LP-11 and LP-19, which mainly target the gp41 pocket site, have greatly improved antiviral potency and stability. In this study, we focused on developing a T20-based lipopeptide inhibitor that lacks pocket-binding sequence and targets a different site.
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!