KNI-102, A NOVEL TRIPEPTIDE HIV PROTEASE INHIBITOR CONTAINING ALLOPHENYLNORSTATINE AS A TRANSITION-STATE MIMIC

Abstract

HIV-1 protease inhibitors containing allophenylnorstatine[Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenyl-butyric acid]-Pro (syn diastereomer) as a transition-state mimic were established to be potent and highly selective. Z-Asn-Apns-Pro-NHBu^t (KNI-102) is the only tripeptide exhibiting substantial anti-HIV activity and may be of minimum size for potent, selective inhibition of HIV protease. Ready availability due to its simple chemical strucuture and stability should make it valuable for studies of the development of metabolically stable anti-AIDS drugs.