1996
DOI: 10.1021/ja953790z
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Substrate-Based Cyclic Peptidomimetics of Phe-Ile-Val That Inhibit HIV-1 Protease Using a Novel Enzyme-Binding Mode

Abstract: Results are presented for inhibitors of HIV-1 protease that demonstrate a new strategy for developing peptidomimetics, involving the replacement of flexible segments of peptide substrates with conformationally constrained hydrolytically-stable macrocyclic structural mimics. A 15-membered macrocycle that imitates the tripeptide PheIle-Val was designed and incorporated into the C-terminus of Ac-Leu-Val-Phe-CHOHCH 2 -{Phe-Ile-Val}-NH 2 , an inhibitor of HIV-1 protease derived from a substrate sequence. Advantages… Show more

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Cited by 73 publications
(82 citation statements)
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“…Cyclic peptides offer great potential as therapeutic agents because they can exhibit membrane permeability, 1 resistance to proteolytic degradation, 2 and metabolic stability 3 . Cyclic peptides also serve as biochemical tools in studying protein-protein interactions and molecular probes.…”
mentioning
confidence: 99%
“…Cyclic peptides offer great potential as therapeutic agents because they can exhibit membrane permeability, 1 resistance to proteolytic degradation, 2 and metabolic stability 3 . Cyclic peptides also serve as biochemical tools in studying protein-protein interactions and molecular probes.…”
mentioning
confidence: 99%
“…[1] Several cyclic peptides that show intriguing biological activity are found in nature. [2] Cyclic peptides have been discovered that are novel antibiotics, [3] enzyme inhibitors, [4] and receptor antagonists. Among them are the smallest cyclopeptides, 2,5-diketopiperazines derivatives, which are commonly found as natural products.…”
mentioning
confidence: 99%
“…50,[70][71][72][73] Some of those macrocycles possess two trans amide bonds and a para substituted aromatic ring within 15-17-membered rings, which can replace tri-or tetrapeptide segments within peptidic substrates and inhibitors. These peptidomimetics fix the receptor bound conformation of bioactive peptides in an extended conformation, which results in functional mimicry.…”
Section: Macrocyclic Peptidomimeticsmentioning
confidence: 99%