KNI-102, a novel tripeptide HIV protease inhibitor containing allophenylnorstatine as a transition-state mimic.

  title={KNI-102, a novel tripeptide HIV protease inhibitor containing allophenylnorstatine as a transition-state mimic.},
  author={Tsutomu Mimoto and Junya Imai and S. Tanaka and Naoko Hattori and Sumitsugu Kisanuki and Kenichi Akaji and Yoshiaki Kiso},
  journal={Chemical \& pharmaceutical bulletin},
  volume={39 11},
HIV-1 protease inhibitors containing allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid]-Pro (syn diastereomer) as a transition-state mimic were established to be potent and highly selective. Z-Asn-Apns-Pro-NHBut (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 structure and stability should make it valuable for studies of… Expand
Design and synthesis of HIV protease inhibitors containing allophenylnorstatine as a transition-state mimic.
  • Y. Kiso
  • Chemistry, Medicine
  • Advances in experimental medicine and biology
  • 1995
The human immunodeficiency virus type-1 codes for a virus-specific aspartic protease responsible for processing the gag and gag-pol polyproteins and for the proliferation of the retrovirus, which provided a basis for the rational design of selective HIV protease-targeted drugs for the treatment of AIDS and related complex. Expand
Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA.
A series of Human Immunodeficiency Virus type-1 protease inhibitors that contain 3-amino-2-hydroxy-4-phenylbutanoic acid (AHPBA) showed enough inhibitory activity toward HIV-1 PR to become prototypes for further structural modification. Expand
Structure of HIV-1 protease with KNI-272, a tight-binding transition-state analog containing allophenylnorstatine.
The structure of the HIV PR/KNI-272 complex illustrates the importance of limiting the conformational degrees of freedom and of using protein-bound water molecules for building potent inhibitors. Expand
Design and synthesis of pseudo-symmetric HIV protease inhibitors containing a novel hydroxymethylcarbonyl (HMC)-hydrazide isostere.
Pseudo-symmetric HIV-1 protease inhibitors containing a novel HMC-hydrazide isostere as the transition-state mimic showed potent inhibitory activity against HIV- 1 protease with nanomolar K(i) values. Expand
Small dipeptide-based HIV protease inhibitors containing the hydroxymethylcarbonyl isostere as an ideal transition-state mimic.
A novel class of HIV protease inhibitors containing an unnatural amino acid, (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid, named allophenylnorstatine, with a hydroxymethylcarbonyl (HMC) isostere is designed and synthesized. Expand
KMI-008, a novel beta-secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-state mimic: design and synthesis of substrate-based octapeptides.
A novel class of substrate-based beta-secretase (BACE1) inhibitors containing a hydroxymethylcarbonyl (HMC) isostere was designed and synthesized and Phenylnorstatine was an effective transition-state mimic at the P(1) position. Expand
Combination of non-natural D-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV protease inhibitors have high efficacy in mutant HIV.
Interestingly, anti-HIV activity of all the D-amino acid-introduced inhibitors was remarkably enhanced in their anti-hIV activities against a Nelfinavir-resistant clone, which has a D30N mutation in the protease, over that of the wild-type strain. Expand
Structure of HIV-1 protease with KNI-272: a transition state mimetic inhibitor containing allophenylnorstatine.
The three dimensional structure of KNI-272 bound to HIV PR, a conformationally-constrained inhibitor containing APNS, has been determined and shown to possess good anti-HIV activity. Expand
Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II.
Based on a highly potent allophenylnorstatine-containing inhibitor, KNI-10006, against the plasmepsins of Plasmodium falciparum, we synthesized a series of tripeptide-type compounds with variousExpand
Structure-activity studies of FIV and HIV protease inhibitors containing allophenylnorstatine.
A new strategy was described for development of bifunctional inhibitors, which combine the protease inhibitor and another enzyme inhibitor in one molecule, and it contains Phe at P3, but no P3' residue. Expand