Synthesis and evaluation of azapeptide-derived inhibitors of serine and cysteine proteases

Todd L. Graybill; Mitchell J. Ross; Bruce R. Gauvin; Jill S. Gregory; Alex L. Harris; Mark A. Ator; James M. Rinker; Roland E. Dolle

doi:10.1016/S0960-894X(00)80516-8

Synthesis and evaluation of azapeptide-derived inhibitors of serine and cysteine proteases

Todd L. Graybill, Mitchell J. Ross, Bruce R. Gauvin, Jill S. Gregory, Alex L. Harris, Mark A. Ator, James M. Rinker, Roland E. Dolle

Center for Drug Discovery

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Azapeptide analogues ii of the α-halomethyl ketones i were synthesized and evaluated as potential inhibitors of serine and cysteine proteases. Inhibitors ii discriminate between the two classes of protease, demonstrating selectivity for cysteine proteases. Azaglycines 1-3 and 5 displayed time-dependent inactivation (k_obs/[I] = 200-1500 M^-1s^-1) of cathepsin B and calpain.

Original language	English
Pages (from-to)	1375-1380
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	2
Issue number	11
DOIs	https://doi.org/10.1016/S0960-894X(00)80516-8
State	Published - Nov 1992

Access to Document

10.1016/S0960-894X(00)80516-8

Cite this

@article{56f99ef0027841e59467346b1224ad82,

title = "Synthesis and evaluation of azapeptide-derived inhibitors of serine and cysteine proteases",

abstract = "Azapeptide analogues ii of the α-halomethyl ketones i were synthesized and evaluated as potential inhibitors of serine and cysteine proteases. Inhibitors ii discriminate between the two classes of protease, demonstrating selectivity for cysteine proteases. Azaglycines 1-3 and 5 displayed time-dependent inactivation (kobs/[I] = 200-1500 M-1s-1) of cathepsin B and calpain.",

author = "Graybill, {Todd L.} and Ross, {Mitchell J.} and Gauvin, {Bruce R.} and Gregory, {Jill S.} and Harris, {Alex L.} and Ator, {Mark A.} and Rinker, {James M.} and Dolle, {Roland E.}",

year = "1992",

month = nov,

doi = "10.1016/S0960-894X(00)80516-8",

language = "English",

volume = "2",

pages = "1375--1380",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

number = "11",

}

TY - JOUR

T1 - Synthesis and evaluation of azapeptide-derived inhibitors of serine and cysteine proteases

AU - Graybill, Todd L.

AU - Ross, Mitchell J.

AU - Gauvin, Bruce R.

AU - Gregory, Jill S.

AU - Harris, Alex L.

AU - Ator, Mark A.

AU - Rinker, James M.

AU - Dolle, Roland E.

PY - 1992/11

Y1 - 1992/11

N2 - Azapeptide analogues ii of the α-halomethyl ketones i were synthesized and evaluated as potential inhibitors of serine and cysteine proteases. Inhibitors ii discriminate between the two classes of protease, demonstrating selectivity for cysteine proteases. Azaglycines 1-3 and 5 displayed time-dependent inactivation (kobs/[I] = 200-1500 M-1s-1) of cathepsin B and calpain.

AB - Azapeptide analogues ii of the α-halomethyl ketones i were synthesized and evaluated as potential inhibitors of serine and cysteine proteases. Inhibitors ii discriminate between the two classes of protease, demonstrating selectivity for cysteine proteases. Azaglycines 1-3 and 5 displayed time-dependent inactivation (kobs/[I] = 200-1500 M-1s-1) of cathepsin B and calpain.

UR - http://www.scopus.com/inward/record.url?scp=0026440452&partnerID=8YFLogxK

U2 - 10.1016/S0960-894X(00)80516-8

DO - 10.1016/S0960-894X(00)80516-8

M3 - Article

AN - SCOPUS:0026440452

SN - 0960-894X

VL - 2

SP - 1375

EP - 1380

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

ER -

Synthesis and evaluation of azapeptide-derived inhibitors of serine and cysteine proteases

Abstract

Access to Document

Other files and links

Fingerprint

Cite this