Facile incorporation of urea pseudopeptides into protease substrate analogue inhibitors |
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Authors: | Myers Adam C Kowalski Jennifer A Lipton Mark A |
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Institution: | Department of Chemistry, Purdue University West Lafayette, IN 47907-2084, USA. |
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Abstract: | A new procedure that employs a one-pot, oxidative Hofmann rearrangement to incorporate a urea linkage into peptide backbones is detailed herein. This methodology was used to replace the scissile peptide bonds of Leu5]enkephalin and a hexapeptide HIV-1 protease substrate. The Leu5]enkephalin analogue was found to inhibit cleavage of hippurylhistidylleucine (HHL) by porcine kidney angiotensin-converting enzyme (PK-ACE) with a 0.88 mM IC50 value, comparable to the Michaelis constant of Leu5]enkephalin with the same enzyme. The HIV-1 protease substrate analogue was shown to inhibit HIV-1 protease with an IC50=34 microM. |
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