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In search of selective inhibitors of cysteine protease, cathepsin K

Wieczerzak, E; Drabik, P; Abrahamson, Magnus LU and Grubb, Anders LU (2005) In International Journal of Peptide Research and Therapeutics 11(3). p.203-209
Abstract
Two potential azapeptide inhibitors of cathepsin K were designed and synthesized. To analyze in detail interactions between these azainhibitors and the investigated cysteine protease, molecular dynamics simulations were performed. For the obtained compounds the equilibrium constants for dissociation of inhibitor-enzyme complex, K-i, were determined. The examined azapeptides proved to be not as potent inhibitors of cathepsin K as they were expected to be according to the results of simulations. However, these calculations provide valuable information about probable structures of this type of peptidomimetics in the catalytic pocket of cathepsin K, which could be useful in designing of more selective inhibitors of this cysteine protease.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cysteine protease, azapeptide, cathepsin K, inhibitor, dynamics, molecular
in
International Journal of Peptide Research and Therapeutics
volume
11
issue
3
pages
203 - 209
publisher
Springer
external identifiers
  • wos:000231889700004
  • scopus:24044434903
ISSN
1573-3904
DOI
10.1007/s10989-005-6791-3
language
English
LU publication?
yes
id
a6167c2b-5f34-4b2f-881d-87d9ebb01372 (old id 224170)
date added to LUP
2007-08-15 16:27:17
date last changed
2017-01-01 04:37:50
@article{a6167c2b-5f34-4b2f-881d-87d9ebb01372,
  abstract     = {Two potential azapeptide inhibitors of cathepsin K were designed and synthesized. To analyze in detail interactions between these azainhibitors and the investigated cysteine protease, molecular dynamics simulations were performed. For the obtained compounds the equilibrium constants for dissociation of inhibitor-enzyme complex, K-i, were determined. The examined azapeptides proved to be not as potent inhibitors of cathepsin K as they were expected to be according to the results of simulations. However, these calculations provide valuable information about probable structures of this type of peptidomimetics in the catalytic pocket of cathepsin K, which could be useful in designing of more selective inhibitors of this cysteine protease.},
  author       = {Wieczerzak, E and Drabik, P and Abrahamson, Magnus and Grubb, Anders},
  issn         = {1573-3904},
  keyword      = {cysteine protease,azapeptide,cathepsin K,inhibitor,dynamics,molecular},
  language     = {eng},
  number       = {3},
  pages        = {203--209},
  publisher    = {Springer},
  series       = {International Journal of Peptide Research and Therapeutics},
  title        = {In search of selective inhibitors of cysteine protease, cathepsin K},
  url          = {http://dx.doi.org/10.1007/s10989-005-6791-3},
  volume       = {11},
  year         = {2005},
}