Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine.

@article{Mimoto1992KynostatinA,
  title={Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine.},
  author={Tsutomu Mimoto and Junya Imai and Sumitsugu Kisanuki and Hiroshi Enomoto and Naoko Hattori and Kenichi Akaji and Yoshiaki Kiso},
  journal={Chemical \& pharmaceutical bulletin},
  year={1992},
  volume={40 8},
  pages={
          2251-3
        }
}
Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition-state mimic were designed and synthesized. Among them, conformationally constrained tripeptide derivatives, kynostatin (KNI)-227 and -272 (Fig. 1), exhibited highly potent antiviral activities against a wide spectrum of HIV isolates. Ready availability due to the simple synthetic procedure and the excellent antiviral properties indicate that KNI… 
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123 Citations
Background Citations
9
Methods Citations
4

123 Citations

Citation Type

Citation Type

Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2/P3 moieties.
Combination of non-natural D-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV protease inhibitors have high efficacy in mutant HIV.
TLDR
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.
KNI-272, a highly selective and potent peptidic HIV protease inhibitor.
  • M. Doi, T. Ishida, Y. Kiso
  • Chemistry
    Acta crystallographica. Section C, Crystal structure communications
  • 2001
TLDR
Kynostatin, a highly selective and potent HIV protease inhibitor containing allophenylnorstatin, has been crystallized as the hydrate from aqueous hexylene glycol and the observed disorder of the phenyl group in the structure is related to the mode of hydration.
HIV-1 protease inhibitors containing a novel C2 symmetrical hydroxyalkylgem-diamino core structure.
TLDR
Two series of peptidomimetics containing a novel C2 symmetrical hydroxyalkylgem-diamino core structure were prepared and evaluated as inhibitors of HIV-1 protease.
Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA.
Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II.
Design and synthesis of HIV protease inhibitors containing allophenylnorstatine as a transition-state mimic.
  • Y. Kiso
  • Biology
    Advances in experimental medicine and biology
  • 1995
TLDR
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.
Synthesis and activity of conformationally-constrained macrocyclic norstatine-based inhibitors of HIV protease
Structure of HIV-1 protease with KNI-272, a tight-binding transition-state analog containing allophenylnorstatine.
Structure-based discovery of Tipranavir disodium (PNU-140690E): a potent, orally bioavailable, nonpeptidic HIV protease inhibitor.
Efforts to develop therapeutically relevant HIV protease inhibitors as medicinal agents in confronting the AIDS crisis have been aided by the wealth of fundamental information acquired during related…
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