Introducing Metallocene into a Triazole Peptide Conjugate Reduces Its Off-rate and Enhances Its Affinity and Antiviral Potency for HIV-1 Gp120

Overview

Journal J Mol Recognit

Specialty Molecular Biology

Date 2008 May 24

PMID 18498083

Citations 22

Authors

Hosahudya Gopi

Simon Cocklin

Vanessa Pirrone

Karyn McFadden

Ferit Tuzer

Isaac Zentner

Sandya Ajith

Sabine Baxter

Navneet Jawanda

Fred C Krebs

Irwin M Chaiken

Affiliations

Soon will be listed here.

Abstract

In this work, we identified a high affinity and potency metallocene-containing triazole peptide conjugate that suppresses the interactions of HIV-1 envelope gp120 at both its CD4 and co-receptor binding sites. The ferrocene-peptide conjugate, HNG-156, was formed by an on-resin copper-catalysed [2+3] cycloaddition reaction. Surface plasmon resonance interaction analysis revealed that, compared to a previously reported phenyl-containing triazole conjugate HNG-105 (105), peptide 156 had a higher direct binding affinity for several subtypes of HIV-1 gp120 due mainly to the decreased dissociation rate of the conjugate-gp120 complex. The ferrocene triazole conjugate bound to gp120 of both clade A (92UG037-08) and clade B (YU-2 and SF162) virus subtypes with nanomolar KD in direct binding and inhibited the binding of gp120 to soluble CD4 and to antibodies that bind to HIV-1YU-2 gp120 at both the CD4 binding site and CD4-induced binding sites. HNG-156 showed a close-to nanomolar IC50 for inhibiting cell infection by HIV-1BaL whole virus. The dual receptor site antagonist activity and potency of HNG-156 make it a promising viral envelope inhibitor lead for developing anti-HIV-1 treatments.

Citing Articles

A Literature Review Focusing on the Antiviral Activity of [1,2,4] and [1,2,3]-triazoles.

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Peptide Triazole Inhibitors of HIV-1: Hijackers of Env Metastability.

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