Journal article
Non-Natural Peptide Triazole Antagonists of HIV-1 Envelope gp120
ChemMedChem, v 8(2), pp 322-328
Feb 2013
PMID: 23239505
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We investigated the derivation of non-natural peptide triazole dual receptor site antagonists of HIV-1 Env gp120 in order to establish a path for developing peptidomimetic antiviral agents. Previously, we found that the peptide triazole HNG-156 (R-I-N-N-I-X-W-S-E-A-M-M-CONH
2
, where
X
is ferrocenyltriazole-Pro (FtP)) had nanomolar binding affinity to gp120, inhibited gp120 binding to CD4 and the co-receptor surrogate
m
Ab 17b and had potent antiviral activity in cell infection assays. Further, truncated variants of HNG-156, typified by UM-24 (Cit-N-N-I-X-W-S-CONH
2
) and containing the critical central stereospecific
L
X-
L
W cluster, retained the functional characteristics of the parent peptide triazole. In the current work, we examined the possibility to replace natural with unnatural residue components in UM-24 to the greatest extent possible. The analogue with the critical “hot spot” residue Trp 6 replaced with
L
-3-Benzothienylalanine (Bta) (KR-41), as well as a completely non-natural analogue containing
D
-amino acid substitutions outside the central cluster (KR-42,
D
Cit-
D
N-
D
N-
D
I-X-Bta-
D
S-CONH
2
), retained the dual receptor site antagonism / antiviral activity signature. The results define differential functional roles of subdomains within the peptide triazole and provide a structural basis for designing metabolically stable peptidomimetic inhibitors of HIV-1 Env gp120.
Metrics
7 Record Views
Details
- Title
- Non-Natural Peptide Triazole Antagonists of HIV-1 Envelope gp120
- Creators
- Kantharaju Kamanna - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Rachna Aneja - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Caitlin Duffy - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Pamela Kubinski - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Diogo Rodrigo Moreira - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Lauren D Bailey - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Karyn McFadden - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Arne Schön - Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218 (USA)Andrew Holmes - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Ferit Tuzer - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Mark Contarino - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15Ernesto Freire - Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218 (USA)Irwin M Chaiken - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N, 15
- Publication Details
- ChemMedChem, v 8(2), pp 322-328
- Publisher
- Wiley
- Grant note
- P01 GM056550 || GM / National Institute of General Medical Sciences : NIGMS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Thomas R. Kline School of Law
- Web of Science ID
- WOS:000314172700015
- Other Identifier
- 991014877922304721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Medicinal
- Pharmacology & Pharmacy