Abstract
We derived macrocyclic HIV-1 antagonists as a new class of peptidomimetic drug leads. Cyclic peptide triazoles (cPTs) retained the gp120 inhibitory and virus-inactivating signature of parent PTs, arguing that cyclization locked an active conformation. The six-residue cPT 9 (AAR029b) exhibited submicromolar antiviral potencies in inhibiting cell infection and triggering gp120 shedding that causes irreversible virion inactivation. Importantly, cPTs were stable to trypsin and chymotrypsin compared to substantial susceptibility of corresponding linear PTs.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry*
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Anti-HIV Agents / pharmacology
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Cell Line
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Chymotrypsin / chemistry
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HIV Envelope Protein gp120 / antagonists & inhibitors*
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HIV-1 / drug effects*
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HIV-1 / physiology
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Humans
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Models, Molecular
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry*
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Oligopeptides / pharmacology
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Peptides, Cyclic / chemical synthesis
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Peptides, Cyclic / chemistry*
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Peptides, Cyclic / pharmacology
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Protein Conformation
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Triazoles / chemical synthesis
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Triazoles / chemistry*
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Triazoles / pharmacology
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Trypsin / chemistry
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Virion / drug effects
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Virion / physiology
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Virus Internalization
Substances
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Anti-HIV Agents
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HIV Envelope Protein gp120
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Oligopeptides
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Peptides, Cyclic
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Triazoles
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Chymotrypsin
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Trypsin