Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L - Comparisons of potency and selectivity profiles with cathepsin B

J.F. Lynas, S.J. Hawthorne, B. Walker

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date
LanguageEnglish
Pages1771-1773
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume10
Issue number15
DOIs
Publication statusPublished - 2000

Fingerprint

Cathepsin L
Cathepsin B
Aldehydes
Cysteine Proteases
Enzyme Inhibitors
Substrate Specificity
Kinetics
Substrates
carbobenzoxyphenylalanine

Cite this

@article{a7abe2446f924518878f54b507cc9c63,
title = "Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L - Comparisons of potency and selectivity profiles with cathepsin B",
abstract = "We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date",
author = "J.F. Lynas and S.J. Hawthorne and B. Walker",
note = "cited By 18",
year = "2000",
doi = "10.1016/S0960-894X(00)00340-1",
language = "English",
volume = "10",
pages = "1771--1773",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier",
number = "15",

}

TY - JOUR

T1 - Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L - Comparisons of potency and selectivity profiles with cathepsin B

AU - Lynas, J.F.

AU - Hawthorne, S.J.

AU - Walker, B.

N1 - cited By 18

PY - 2000

Y1 - 2000

N2 - We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date

AB - We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date

U2 - 10.1016/S0960-894X(00)00340-1

DO - 10.1016/S0960-894X(00)00340-1

M3 - Article

VL - 10

SP - 1771

EP - 1773

JO - Bioorganic and Medicinal Chemistry Letters

T2 - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 15

ER -