Substrate and inhibitor studies on proteinase 3

Chih Min Kam; John E. Kerrigan; Koert M. Dolman; Roel Goldschmeding; Albert E.G.Kr Von dem Borne; James C. Powers

doi:10.1016/0014-5793(92)80340-M

Substrate and inhibitor studies on proteinase 3

Chih Min Kam
, John E. Kerrigan
, Koert M. Dolman
, Roel Goldschmeding
, Albert E.G.Kr Von dem Borne
, James C. Powers^*

^*Corresponding author for this work

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

57 Citations (Scopus)

Abstract

Various amino acid and peptide thioesters were tested as substrates for human proteinase 3 and the best substrate is Boc-Ala-Ala-Nva-SBzl with a k_cal/K_m value of 1.0 × 10⁶nM^it-1s^it-1 Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with k_cal/K_m values of (1-4) × 10⁵ M^-1 s^-1. Substituted isocoumarins are potent inhibitors of proteinase 3 and the best inhibitors are 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarin and 3.4-dichloroisocoumarin (DCI) with k_obs/[I] values of 4700 and 2600 M^-1 s^-1, respectively. Substituted isocoumarins. peptide phosphonates and chloromethyl ketones inhibited proteinase 3 less potently than human neutrophil elastase (HNE) by 1-2 orders of magnitude.

Original language	English
Pages (from-to)	119-123
Number of pages	5
Journal	FEBS letters
Volume	297
Issue number	1-2
DOIs	https://doi.org/10.1016/0014-5793(92)80340-M
Publication status	Published - 3 Feb 1992
Externally published	Yes

Keywords

Peptide chloromethyl ketone
Peptide phosphonate
Peptide thioester
Proteinase 3
Substituted isocoumarin

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10.1016/0014-5793(92)80340-M

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title = "Substrate and inhibitor studies on proteinase 3",

abstract = "Various amino acid and peptide thioesters were tested as substrates for human proteinase 3 and the best substrate is Boc-Ala-Ala-Nva-SBzl with a kcal/Km value of 1.0 × 106nMit-1sit-1 Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with kcal/Km values of (1-4) × 105 M-1 s-1. Substituted isocoumarins are potent inhibitors of proteinase 3 and the best inhibitors are 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarin and 3.4-dichloroisocoumarin (DCI) with kobs/[I] values of 4700 and 2600 M-1 s-1, respectively. Substituted isocoumarins. peptide phosphonates and chloromethyl ketones inhibited proteinase 3 less potently than human neutrophil elastase (HNE) by 1-2 orders of magnitude.",

keywords = "Peptide chloromethyl ketone, Peptide phosphonate, Peptide thioester, Proteinase 3, Substituted isocoumarin",

author = "Kam, \{Chih Min\} and Kerrigan, \{John E.\} and Dolman, \{Koert M.\} and Roel Goldschmeding and \{Von dem Borne\}, \{Albert E.G.Kr\} and Powers, \{James C.\}",

year = "1992",

month = feb,

day = "3",

doi = "10.1016/0014-5793(92)80340-M",

language = "English",

volume = "297",

pages = "119--123",

journal = "FEBS letters",

issn = "0014-5793",

publisher = "John Wiley \& Sons Inc.",

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TY - JOUR

T1 - Substrate and inhibitor studies on proteinase 3

AU - Kam, Chih Min

AU - Kerrigan, John E.

AU - Dolman, Koert M.

AU - Goldschmeding, Roel

AU - Von dem Borne, Albert E.G.Kr

AU - Powers, James C.

PY - 1992/2/3

Y1 - 1992/2/3

N2 - Various amino acid and peptide thioesters were tested as substrates for human proteinase 3 and the best substrate is Boc-Ala-Ala-Nva-SBzl with a kcal/Km value of 1.0 × 106nMit-1sit-1 Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with kcal/Km values of (1-4) × 105 M-1 s-1. Substituted isocoumarins are potent inhibitors of proteinase 3 and the best inhibitors are 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarin and 3.4-dichloroisocoumarin (DCI) with kobs/[I] values of 4700 and 2600 M-1 s-1, respectively. Substituted isocoumarins. peptide phosphonates and chloromethyl ketones inhibited proteinase 3 less potently than human neutrophil elastase (HNE) by 1-2 orders of magnitude.

AB - Various amino acid and peptide thioesters were tested as substrates for human proteinase 3 and the best substrate is Boc-Ala-Ala-Nva-SBzl with a kcal/Km value of 1.0 × 106nMit-1sit-1 Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with kcal/Km values of (1-4) × 105 M-1 s-1. Substituted isocoumarins are potent inhibitors of proteinase 3 and the best inhibitors are 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarin and 3.4-dichloroisocoumarin (DCI) with kobs/[I] values of 4700 and 2600 M-1 s-1, respectively. Substituted isocoumarins. peptide phosphonates and chloromethyl ketones inhibited proteinase 3 less potently than human neutrophil elastase (HNE) by 1-2 orders of magnitude.

KW - Peptide chloromethyl ketone

KW - Peptide phosphonate

KW - Peptide thioester

KW - Proteinase 3

KW - Substituted isocoumarin

UR - https://www.scopus.com/pages/publications/0026516023

U2 - 10.1016/0014-5793(92)80340-M

DO - 10.1016/0014-5793(92)80340-M

M3 - Article

C2 - 1551417

AN - SCOPUS:0026516023

SN - 0014-5793

VL - 297

SP - 119

EP - 123

JO - FEBS letters

JF - FEBS letters

IS - 1-2

ER -

Substrate and inhibitor studies on proteinase 3

Abstract

Keywords

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