Potent and Selective Inactivation of Cysteine Proteinases with N-peptidyl-O-acyl Hydroxylamines

Overview

Journal Biochem J

Specialty Biochemistry

Date 1989 Nov 1

PMID 2574571

Citations 2

Authors

D Bromme

A Schierhorn

H KIRSCHKE

B Wiederanders

A Barth

S FITTKAU

H U Demuth

Affiliations

Soon will be listed here.

Abstract

A series of N-peptidyl-O-acyl hydroxylamines was synthesized and tested as inactivators of cysteine proteinases. Depending on the structure of the peptidyl residue of the inhibitors, rapid and complete irreversible inactivation of the lysosomal cathepsins, B, L and S, may be achieved. The most effective inhibitors display second-order rate constants of the inactivation in the range 10(5)-10(6) M-1.s-1. By contrast, the activity of the aminoendopeptidase cathepsin H is only negligibly affected by the N-terminal-protected peptidyl inhibitors.

Citing Articles

A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L.

Dana D, Pathak S Molecules. 2020; 25(3).

PMID: 32041276 PMC: 7038230. DOI: 10.3390/molecules25030698.

Peptidyl vinyl sulphones: a new class of potent and selective cysteine protease inhibitors: S2P2 specificity of human cathepsin O2 in comparison with cathepsins S and L.

Bromme D, Klaus J, Okamoto K, Rasnick D, PALMER J Biochem J. 1996; 315 ( Pt 1):85-9.

PMID: 8670136 PMC: 1217200. DOI: 10.1042/bj3150085.

References

Schechter I, Berger A . On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun. 1967; 27(2):157-62. DOI: 10.1016/s0006-291x(67)80055-x. View

Kitz R, Wilson I . Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem. 1962; 237:3245-9. View

KIRSCHKE H, Langner J, Wiederanders B, Ansorge S, Bohley P . Cathepsin L. A new proteinase from rat-liver lysosomes. Eur J Biochem. 1977; 74(2):293-301. DOI: 10.1111/j.1432-1033.1977.tb11393.x. View

KIRSCHKE H, Shaw E . Rapid interaction of cathepsin L by Z-Phe-PheCHN12 and Z-Phe-AlaCHN2. Biochem Biophys Res Commun. 1981; 101(2):454-8. DOI: 10.1016/0006-291x(81)91281-x. View

Tian W, Tsou C . Determination of the rate constant of enzyme modification by measuring the substrate reaction in the presence of the modifier. Biochemistry. 1982; 21(5):1028-32. DOI: 10.1021/bi00534a031. View

Barrett A, KIRSCHKE H . Cathepsin B, Cathepsin H, and cathepsin L. Methods Enzymol. 1981; 80 Pt C:535-61. DOI: 10.1016/s0076-6879(81)80043-2. View

KIRSCHKE H, Kembhavi A, Bohley P, Barrett A . Action of rat liver cathepsin L on collagen and other substrates. Biochem J. 1982; 201(2):367-72. PMC: 1163652. DOI: 10.1042/bj2010367. View

Fischer G, Demuth H, Barth A . N,O-diacylhydroxylamines as enzyme-activated inhibitors for serine proteases. Pharmazie. 1983; 38(4):249-50. DOI: 10.1002/chin.198341334. View

Mason R, Taylor M, Etherington D . The purification and properties of cathepsin L from rabbit liver. Biochem J. 1984; 217(1):209-17. PMC: 1153198. DOI: 10.1042/bj2170209. View

10.

Schon E, Demuth H, Barth A, Ansorge S . Dipeptidyl peptidase IV of human lymphocytes. Evidence for specific hydrolysis of glycylproline p-nitroanilide in T-lymphocytes. Biochem J. 1984; 223(1):255-8. PMC: 1144287. DOI: 10.1042/bj2230255. View

11.

Delaisse J, Eeckhout Y, Vaes G . In vivo and in vitro evidence for the involvement of cysteine proteinases in bone resorption. Biochem Biophys Res Commun. 1984; 125(2):441-7. DOI: 10.1016/0006-291x(84)90560-6. View

12.

Mason R, Johnson D, Barrett A, Chapman H . Elastinolytic activity of human cathepsin L. Biochem J. 1986; 233(3):925-7. PMC: 1153120. DOI: 10.1042/bj2330925. View

13.

KIRSCHKE H, Schmidt I, Wiederanders B . Cathepsin S. The cysteine proteinase from bovine lymphoid tissue is distinct from cathepsin L (EC 3.4.22.15). Biochem J. 1986; 240(2):455-9. PMC: 1147438. DOI: 10.1042/bj2400455. View

14.

Bromme D, Bescherer K, KIRSCHKE H, FITTKAU S . Enzyme-substrate interactions in the hydrolysis of peptides by cathepsins B and H from rat liver. Biochem J. 1987; 245(2):381-5. PMC: 1148133. DOI: 10.1042/bj2450381. View

15.

Schon E, Jahn S, Kiessig S, Demuth H, Neubert K, Barth A . The role of dipeptidyl peptidase IV in human T lymphocyte activation. Inhibitors and antibodies against dipeptidyl peptidase IV suppress lymphocyte proliferation and immunoglobulin synthesis in vitro. Eur J Immunol. 1987; 17(12):1821-6. DOI: 10.1002/eji.1830171222. View

16.

KIRSCHKE H, Wikstrom P, Shaw E . Active center differences between cathepsins L and B: the S1 binding region. FEBS Lett. 1988; 228(1):128-30. DOI: 10.1016/0014-5793(88)80600-8. View

17.

Denhardt D, Greenberg A, Egan S, Hamilton R, Wright J . Cysteine proteinase cathepsin L expression correlates closely with the metastatic potential of H-ras-transformed murine fibroblasts. Oncogene. 1987; 2(1):55-9. View

18.

Zumbrunn A, Stone S, Shaw E . Synthesis and properties of Cbz-Phe-Arg-CHN2 (benzyloxycarbonylphenylalanylarginyldiazomethane) as a proteinase inhibitor. Biochem J. 1988; 250(2):621-3. PMC: 1148900. DOI: 10.1042/bj2500621. View

19.

Crawford C, Mason R, Wikstrom P, Shaw E . The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathepsin L and cathepsin B. Biochem J. 1988; 253(3):751-8. PMC: 1149367. DOI: 10.1042/bj2530751. View

20.

Smith R, Coles P, SPENCER R, Copp L, Jones C, Krantz A . Peptidyl O-acyl hydroxamates: potent new inactivators of cathepsin B. Biochem Biophys Res Commun. 1988; 155(3):1201-6. DOI: 10.1016/s0006-291x(88)81267-1. View