Advertisement
Advertise here Publish your press releases here Sponsor BioPortfolio
Follow us on Twitter Sign up for daily news and research emails Contributors wanted

Increase of anti-HIV activity of C-peptide fusion inhibitors using a bivalent drug design approach.

07:27 EDT 31st July 2014 | BioPortfolio

Summary of "Increase of anti-HIV activity of C-peptide fusion inhibitors using a bivalent drug design approach."

We reported the design of fusion inhibitors with improved activity using a multivalent inhibitor design strategy. First, we chose C29 as the template sequence, which is a 29-mer peptide derived from HIV-1 gp41 CHR domain and has anti-HIV activity of IC50 118nM in a cell-cell fusion assay. We optimized the crosslink sites and linkers of the template peptide. We found that N-terminal crosslink caused activity improvement based on the multivalent co-operative effect. Especially, the IC50 of peptide (CAcaC29)2 was improved from 49.02 (monomeric form) to 5.71nM. Compared with long peptides, short peptides may be more suitable to analyze the co-operative effect. So we selected a shorter peptide C22 to synthesize the bivalent inhibitors. Due its weak helicity, no co-operative effect appeared. Therefore, we chose SC22EK, which were introduced salt bridges to consolidate the helicity based on the natural sequence C22. The cross-linked (CAcaSC22EK)2 was four times more potent than the monomer SC22EK in anti-HIV activity, with an IC50 value of 4.92nM close to the high active peptide fusion inhibitor C34. The strategy used in this study may be used to design new fusion inhibitors to interfere similar processes.

Affiliation

Beijing Institute of Pharmacology & Toxicology, Pharmaceutical Chemistry, 27 Taiping Road, Beijing 100850, China.

Journal Details

This article was published in the following journal.

Name: Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Pages:

Links

PubMed Articles [20272 Associated PubMed Articles listed on BioPortfolio]

Inhibition of arenavirus infection by a glycoprotein-derived peptide with a novel mechanism.

The family Arenaviridae includes a number of viruses of public health importance, such as the Category A hemorrhagic fever viruses Lassa, Junin, Machupo, Guanarito, and Sabia. Current chemotherapy for...

The use of hairpin DNA duplexes as HIV-1 fusion inhibitors: Synthesis, characterization, and activity evaluation.

Discovery of new drugs for the treatment of AIDS that possess unique structures associated with novel mechanisms of action are of great importance due the rapidity with which drug-resistant HIV-1 stra...

Development of HIV-1 Fusion Inhibitors Targeting gp41.

The HIV-1 envelope protein glycoprotein 41 (gp41) is crucial in the HIV-1 infection process, therefore gp41 has emerged as an attractive target for drug design against AIDS. During the past decades, t...

Recombinant approach for the production of HIV fusion inhibitor Enfuvirtide using Escherichia coli.

The use of antiretroviral drugs is gaining importance in the recent past for the treatment of human immunodeficiency virus infection. Enfuvirtide (T20) is one of the fusion inhibitors, inhibits the fu...

The M-T hook structure increases the potency of HIV-1 fusion inhibitor sifuvirtide and overcomes drug resistance.

Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1 gp41 are potent fusion inhibitors. We have recently demonstrated that the unique M-T hook structure preceding the pocket-binding motif...

Clinical Trials [3475 Associated Clinical Trials listed on BioPortfolio]

Vaccine Therapy in Preventing Cytomegalovirus in Healthy Participants

RATIONALE: Vaccines made from peptides may help the body build an immune response to kill cytomegalovirus. PURPOSE: This phase I trial is studying the side effects and best dose of vaccin...

Randomized, Phase I/II, Dose-Ranging, Open-Label Trial of the Anti-HIV Activity of Delavirdine Mesylate (DLV; U-90,152S)

PRIMARY: To study the safety and tolerance of delavirdine mesylate ( U-90152 ) monotherapy. To compare the anti-HIV activity of three blood concentration levels of this agent with nucleosi...

Pilot Study to Assess Safety/Prelimary Effectiveness of Prefix in Subjects With Degenerative Disc Disease (DDD) Undergoing Spine Fusion Surgery

This is a pilot study to evaulate the safety and prelimary effectiveness of Prefix as compared to autogenous bone for spinal fusion procedures in skeletally mature subjects with degenerati...

Safety and Immunogenicity of Formulations of Dengue Vaccines in Healthy Flavivirus-Naïve Adults

This is part of an ongoing effort to develop a satisfactory dengue vaccine: Primary objective: To describe the safety after each vaccination with bivalent and tetravalent formulations of...

A Study of a Bivalent Influenza Peptide Conjugate Vaccine in Healthy Adults

This is a first in man study evaluating the tolerability and immunogenicity of BIPCV/IMX (V512) at increasing concentrations of influenza viral peptides A/M2+B/HA0 peptides and IMX, a sapo...

Medical and Biotech [MESH] Definitions

Inhibitors of the fusion of HIV to host cells, preventing viral entry. This includes compounds that block attachment of HIV ENVELOPE PROTEIN GP120 to CD4 RECEPTORS.

Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.

Circulating 38-kDa proteins that are internal peptide fragments of PLASMINOGEN. The name derives from the fact that they are potent ANGIOGENESIS INHIBITORS. Angiostatins contain four KRINGLE DOMAINS which are associated with their potent angiostatic activity.

A 36-amino acid peptide present in many organs and in many sympathetic noradrenergic neurons. It has vasoconstrictor and natriuretic activity and regulates local blood flow, glandular secretion, and smooth muscle activity. The peptide also stimulates feeding and drinking behavior and influences secretion of pituitary hormones.

Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).

Search BioPortfolio:
Advertisement
Advertisement

Searches Linking to this Article