Journal article
Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120
Journal of molecular recognition, v 22(2)
2009
PMID: 18498083
Featured in Collection : UN Sustainable Development Goals @ Drexel
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
K
D
in direct binding and inhibited the binding of gp120 to soluble CD4 and to antibodies that bind to HIV-1
YU-2
gp120 at both the CD4 binding site and CD4-induced binding sites. HNG-156 showed a close-to nanomolar IC
50
for inhibiting cell infection by HIV-1
BaL
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.
Metrics
Details
- Title
- Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120
- Creators
- Hosahudya Gopi - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USASimon Cocklin - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USAVanessa Pirrone - Department of Microbiology and Immunology, and Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USAKaryn McFadden - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USAFerit Tuzer - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USAIsaac Zentner - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USASandya Ajith - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USASabine Baxter - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USANavneet Jawanda - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USAFred C Krebs - Department of Microbiology and Immunology, and Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USAIrwin M Chaiken - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
- Publication Details
- Journal of molecular recognition, v 22(2)
- Publisher
- Wiley
- Grant note
- U01 AI067854 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology
- Web of Science ID
- WOS:000263566400016
- Scopus ID
- 2-s2.0-63449085889
- Other Identifier
- 991014877857604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics