Arginine-based structures are specific inhibitors of cathepsin C. Application of peptide combinatorial libraries
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
10824120
DOI
10.1046/j.1432-1327.2000.01364.x
PII: ejb1364
Knihovny.cz E-zdroje
- MeSH
- arginin chemie MeSH
- inhibitory cysteinových proteinas chemie farmakologie MeSH
- kathepsin C antagonisté a inhibitory MeSH
- peptidy farmakologie MeSH
- racionální návrh léčiv MeSH
- skot MeSH
- techniky kombinatorické chemie MeSH
- vazebná místa účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- arginin MeSH
- inhibitory cysteinových proteinas MeSH
- kathepsin C MeSH
- peptidy MeSH
- polyarginine MeSH Prohlížeč
Novel synthetic peptide inhibitors of lysosomal cysteine proteinase cathepsin C have been designed through the use of soluble peptide combinatorial libraries. The uncovered structural inhibitory module consists of the N-terminal cluster of L-arginine residues. Its modification with D-amino acids or arginine derivatives did not increase the inhibition strength. Inhibitory potency of oligoarginines improves with the elongation of peptide chain reaching a maximum for octa-L-arginine. The oligoarginines specifically interact with the cathepsin C active site as shown by competitive-type inhibition kinetics (Ki approximately 10-5 M) and intrinsic fluorescence measurements. The inhibitory interaction of oligoarginines is established through the specific spatial contact of a net of guanidino groups in the arginine side-chains, as indicated by comparison with inhibitory action of low molecular mass guanidine derivatives (Ki approximately 10-3 M). Nonarginine polyionic compounds cannot mimic the inhibitory effect of oligoarginines. The arginine-based peptide inhibitors were selective towards cathepsin C among other cysteine proteinases tested.
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