In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine

@article{Kageyama1993InVA,
  title={In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine},
  author={Seiji Kageyama and Tsutomu Mimoto and Yasuhiro Murakawa and Motoyoshi Nomizu and H. Jun. Ford and Takuma Shirasaka and Sergei V. Gulnik and John W. Erickson and Kanji Takada and Hideya Hayashi},
  journal={Antimicrobial Agents and Chemotherapy},
  year={1993},
  volume={37},
  pages={810 - 817}
}
Transition state mimetic tripeptide human immunodeficiency virus (HIV) protease inhibitors containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were synthesized and tested for activity against HIV in vitro. Two compounds, KNI-227 and KNI-272, which were highly potent against HIV protease with little inhibition of other aspartic proteases, showed the most potent activity against the infectivity and cytopathic effect of a wide spectrum of HIV strains. As tested in… 
Structure of HIV-1 protease with KNI-272: a transition state mimetic inhibitor containing allophenylnorstatine.
TLDR
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.
Protein binding of human immunodeficiency virus protease inhibitor KNI-272 and alteration of its in vitro antiretroviral activity in the presence of high concentrations of proteins.
TLDR
High levels of KNI-272 in plasma may be required when this compound undergoes clinical trials relative to those inferred from in vitro data involving the use of 10 to 15% FCS-containing culture media, as detailed studies of the protein binding suggest.
JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1.
TLDR
Structural analysis revealed that the presence of a flexible P2' moiety is important for the potency of JE-2147 toward wild-type and mutant viruses, and suggest that the use of flexible components may open a new avenue for designing PIs that resist the emergence of PI-resistant HIV-1.
Design of small peptidomimetic HIV-1 protease inhibitors and prodrug forms
TLDR
A novel prodrug-type anti-HIV agent — the conjugate of a peptidomimetic HIV-1 protease inhibitor containing a free carboxylic acid with a nucleoside reverse transcriptase inhibitor is designed and synthesized.
Inhibition of Acute-, Latent-, and Chronic-Phase Human Immunodeficiency Virus Type 1 (HIV-1) Replication by a Bistriazoloacridone Analog That Selectively Inhibits HIV-1 Transcription
TLDR
Demonstration of in vivo anti-HIV-1 activity by temacrazine identifies bistriazoloacridones as a new class of pharmaceuticals that selectively blocks HIV-1 transcription.
Design and synthesis of substrate-based peptidomimetic human immunodeficiency virus protease inhibitors containing the hydroxymethylcarbonyl isostere.
  • Y. Kiso
  • Biology, Chemistry
    Biopolymers
  • 1996
The human immunodeficiency (HIV) codes for an aspartic protease known to be essential for retroviral maturation and replication. The HIV protease can recognize Phe-Pro and Tyr-Pro sequences as the
Small dipeptide-based HIV protease inhibitors containing the hydroxymethylcarbonyl isostere as an ideal transition-state mimic.
TLDR
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.
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