Advanced

Synthesis of cysteine proteinase inhibitors structurally based on the proteinase interacting N-terminal region of human cystatin C

Grubb, Anders LU ; Abrahamson, Magnus LU ; Olafsson, I; Trojnar, J; Kasprzykowska, R; Kasprzykowski, F and Grzonka, Z (1990) In Biological Chemistry Hoppe-Seyler 371(Suppl.). p.137-144
Abstract
Peptides spanning the entire, or part of, the Gly4-Glu21 segment of the human cysteine proteinase inhibitor cystatin C have been synthesized. Peptides containing residues on the N-terminal side of Gly11 were rapidly cleaved by papain at the bond Gly11-Gly12 whereas a peptide starting at residue Gly11 was not, thus demonstrating 1. that the N-terminal segment of cystatin C has an amino acid sequence that would allow rapid interaction between this segment and the substrate pocket of papain and, if this interaction takes place, that 2. the cystatin C residue Gly11 would be in the P1 position, and 3. the major interaction would be between residues Arg8-Val10 and the papain substrate pocket subsites S4, S3 and S2, respectively. Several modified... (More)
Peptides spanning the entire, or part of, the Gly4-Glu21 segment of the human cysteine proteinase inhibitor cystatin C have been synthesized. Peptides containing residues on the N-terminal side of Gly11 were rapidly cleaved by papain at the bond Gly11-Gly12 whereas a peptide starting at residue Gly11 was not, thus demonstrating 1. that the N-terminal segment of cystatin C has an amino acid sequence that would allow rapid interaction between this segment and the substrate pocket of papain and, if this interaction takes place, that 2. the cystatin C residue Gly11 would be in the P1 position, and 3. the major interaction would be between residues Arg8-Val10 and the papain substrate pocket subsites S4, S3 and S2, respectively. Several modified peptide derivatives containing either diazomethane groups or peptide bond isosters were synthesized based on the structure of the Leu9-Gly11 segment of cystatin C and tested for their cysteine proteinase inhibiting capacity. The peptidyl derivatives, t-butyloxycarbonyl-valyl-glycyl-diazomethane and benzyloxycarbonyl-leucyl-valyl-glycyl-diazomethane irreversible inhibited the cysteine proteinases papain, bovine cathepsin B and streptococcal proteinase, but did not influence the activity of serine, aspartic or metallo-proteinases. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biological Chemistry Hoppe-Seyler
volume
371
issue
Suppl.
pages
137 - 144
publisher
De Gruyter
external identifiers
  • pmid:2400574
  • scopus:0025002171
ISSN
0177-3593
language
English
LU publication?
yes
id
33c01a53-396d-4c97-8d1b-253209df076a (old id 1105545)
date added to LUP
2008-08-06 08:12:30
date last changed
2017-08-27 05:29:54
@article{33c01a53-396d-4c97-8d1b-253209df076a,
  abstract     = {Peptides spanning the entire, or part of, the Gly4-Glu21 segment of the human cysteine proteinase inhibitor cystatin C have been synthesized. Peptides containing residues on the N-terminal side of Gly11 were rapidly cleaved by papain at the bond Gly11-Gly12 whereas a peptide starting at residue Gly11 was not, thus demonstrating 1. that the N-terminal segment of cystatin C has an amino acid sequence that would allow rapid interaction between this segment and the substrate pocket of papain and, if this interaction takes place, that 2. the cystatin C residue Gly11 would be in the P1 position, and 3. the major interaction would be between residues Arg8-Val10 and the papain substrate pocket subsites S4, S3 and S2, respectively. Several modified peptide derivatives containing either diazomethane groups or peptide bond isosters were synthesized based on the structure of the Leu9-Gly11 segment of cystatin C and tested for their cysteine proteinase inhibiting capacity. The peptidyl derivatives, t-butyloxycarbonyl-valyl-glycyl-diazomethane and benzyloxycarbonyl-leucyl-valyl-glycyl-diazomethane irreversible inhibited the cysteine proteinases papain, bovine cathepsin B and streptococcal proteinase, but did not influence the activity of serine, aspartic or metallo-proteinases.},
  author       = {Grubb, Anders and Abrahamson, Magnus and Olafsson, I and Trojnar, J and Kasprzykowska, R and Kasprzykowski, F and Grzonka, Z},
  issn         = {0177-3593},
  language     = {eng},
  number       = {Suppl.},
  pages        = {137--144},
  publisher    = {De Gruyter},
  series       = {Biological Chemistry Hoppe-Seyler},
  title        = {Synthesis of cysteine proteinase inhibitors structurally based on the proteinase interacting N-terminal region of human cystatin C},
  volume       = {371},
  year         = {1990},
}