| 1. |
- Grubb, Anders, et al.
(author)
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Synthesis of cysteine proteinase inhibitors structurally based on the proteinase interacting N-terminal region of human cystatin C
- 1990
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In: Biological Chemistry Hoppe-Seyler. - 0177-3593. ; 371:Suppl., s. 137-144
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Journal article (peer-reviewed)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.
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| 2. |
- Johansson, L, et al.
(author)
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A peptidyl derivative structurally based on the inhibitory center of cystatin C inhibits bone resorption in vitro
- 2000
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In: Bone. - 1873-2763. ; 26:5, s. 451-459
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Journal article (peer-reviewed)abstract
- Human cystatin C is a cysteine proteinase inhibitor belonging to the cystatin superfamily, which previously has been shown to inhibit bone resorption in bone organ culture. The aminoterminal segment, Arg8-Leu9-Val10-Gly11 (RLVG), of the single polypeptide chain of cystatin C constitutes an essential part of its inhibitory center. In the present study, the effect of benzyloxycarbonyl-Arg8-Leu9-Val10-Gly11-diazomethane (Z-RLVG-CHN2) on bone resorption in vitro was compared with the effects of cystatin C and calcitonin. Bone resorption was assessed by the release of 45Ca and 3H from mouse calvarial bones prelabeled with [45Ca]CaCl2 and [3H]-proline, respectively. Z-RLVG-CHN2 concentration-dependently inhibited the release of 45Ca and 3H in bones stimulated by parathyroid hormone (PTH), with half-maximal inhibition obtained at 1 μmol/L. The inhibitory actions of Z-RLVG-CHN2 and cystatin C were persistent, whereas action induced initially by calcitonin was lost with time. The inhibition caused by Z-RLVG-CHN2 and cystatin C on PTH-stimulated 45Ca release was observed after 6 h, whereas inhibition by calcitonin was seen already after 2 h. In contrast, the inhibitory effects of Z-RLVG-CHN2 and cystatin C, as well as that of calcitonin, on 3H release was seen already after 2 h. Z-RLVG-CHN2, in which the reactive carboxyterminal diazomethane was substituted by nonreactive groups [−OH, −NH2, or −N(CH3)2], resulted in peptidyl derivatives, which, in contrast to Z-RLVG-CHN2 and cystatin C, inhibited neither cysteine proteinases nor bone resorption. In contrast to wild-type cystatin C, recombinant human cystatin C with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106, and with low or nonexistent affinity for cysteine proteinases, did not display any inhibitory effect on bone resorption. These data strongly indicate that Z-RLVG-CHN2 inhibits bone resorption in vitro by a mechanism that seems primarily to be due to an inhibition of bone matrix degradation via cysteine proteinases. The data also corroborate the hypothesis that cystatin C inhibits bone resorption by virtue of its cysteine proteinase inhibitory capacity.
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| 3. |
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| 4. |
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| 5. |
- Kasprzykowski, F., et al.
(author)
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Peptidyl diazomethylketones as cysteine protease inhibitors structurally based upon the inhibitory centers of cystatins
- 2001
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In: Polish Journal of Chemistry. - 0137-5083. ; 75:6, s. 831-837
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Journal article (peer-reviewed)abstract
- Six new putative cysteine protease inhibitors based upon sequences of the N-terminal binding fragments of rat cystatin A, bovine cystatin C and human cystatins D and S were synthesized, inhibitory activities of these compounds against papain and bovine cathepsin B were tested. Additionally, agar well diffusion test of their antibacterial activity against Streptococcus pyogenes was performed.
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| 6. |
- Lerner, Ulf H, et al.
(author)
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Cysteine proteinases in osteoclast function and recruitment
- 2004
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In: Biological Mechanisms of Tooth Movement and Craniofacial Adaptation. - Boston, Massachusetts, USA : Harvard Society for the Advancement of Orthodontics. - 0963204750 ; , s. 227-227
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Book chapter (other academic/artistic)
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| 7. |
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