PMID- 8403085
OWN - NLM
STAT- MEDLINE
DCOM- 19931124
LR  - 20190706
IS  - 0009-2363 (Print)
IS  - 0009-2363 (Linking)
VI  - 41
IP  - 8
DP  - 1993 Aug
TI  - Studies of HIV-1 protease inhibitors. I. Incorporation of a reduced peptide, 
      simple aminoalcohol, and statine analog at the scissile site of substrate 
      sequences.
PG  - 1369-77
AB  - Inhibitors of the protease of human immunodeficiency virus type-1 (HIV-1) were 
      designed and synthesized. A reduced peptide, simple aminoalcohol, and statine 
      analog, 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), were inserted at the 
      scissile site of substrate sequences of HIV-1 protease. While both reduced 
      peptides and simple aminoalcohol derivatives were weak inhibitors, the peptides 
      containing AHPPA demonstrated moderate inhibitory activity. The more potent 
      alcohol configuration of AHPPA is (R), which is opposite to the configuration in 
      potent inhibitors of other aspartic proteases. In particular, compound 28 
      ((3R,4S)-4-(N-tert-butoxycarbonyl- 
      L-glutaminyl-L-asparaginyl)amino-3-hydroxy-5-phenylpentanoic acid 
      2'-methylbutylamide) had a Ki of 0.36 microM and exhibited excellent enzyme 
      specificity.
FAU - Sakurai, M
AU  - Sakurai M
AD  - New Lead Research Laboratory, Sankyo Co., Ltd., Tokyo, Japan.
FAU - Sugano, M
AU  - Sugano M
FAU - Handa, H
AU  - Handa H
FAU - Komai, T
AU  - Komai T
FAU - Yagi, R
AU  - Yagi R
FAU - Nishigaki, T
AU  - Nishigaki T
FAU - Yabe, Y
AU  - Yabe Y
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Chem Pharm Bull (Tokyo)
JT  - Chemical & pharmaceutical bulletin
JID - 0377775
RN  - 0 (Amino Acids)
RN  - 0 (Amino Alcohols)
RN  - 0 (HIV Protease Inhibitors)
RN  - 0 (Peptides)
RN  - 72155-51-2 (4-amino-3-hydroxy-5-phenylpentanoic acid)
RN  - YTC77XR1EK (statine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acids/*chemistry/pharmacology
MH  - Amino Alcohols/*chemistry
MH  - HIV Protease Inhibitors/*chemistry/pharmacology
MH  - HIV-1/*enzymology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Oxidation-Reduction
MH  - Peptides/*chemistry
MH  - Substrate Specificity
EDAT- 1993/08/01 00:00
MHDA- 1993/08/01 00:01
CRDT- 1993/08/01 00:00
PHST- 1993/08/01 00:00 [pubmed]
PHST- 1993/08/01 00:01 [medline]
PHST- 1993/08/01 00:00 [entrez]
AID - 10.1248/cpb.41.1369 [doi]
PST - ppublish
SO  - Chem Pharm Bull (Tokyo). 1993 Aug;41(8):1369-77. doi: 10.1248/cpb.41.1369.