A novel constrained reduced-amide inhibitor of HIV-1 protease derived from the sequential incorporation of. gamma.-turn mimetics into a model substrate

…, JF Callahan, ML Moore, TA Tomaszek Jr…

Index: Newlander; Callahan; Moore; Tomaszek Jr.; Huffman Journal of Medicinal Chemistry, 1993 , vol. 36, # 16 p. 2321 - 2331

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Citation Number: 48

Abstract

C7 mimetics, designed to lock three amino acid residues of a peptide chain into a y-turn conformation, were introduced sequentially between the P3 to Pi positions of a model HIV-1 protease substrate I (resulting in compounds 11-IV) to probe its conformational requirements in binding to HIV-1 protease. Of these, compound IIIa with the C7 mimetic replacing Asn-Tyr- Pro, corresponding to the PZ through Pi positions of substrate, was found to be an inhibitor ...