摘要 |
<p>New pseudopeptide or derivatized peptide compounds (I) (preferably having 4-8 amino acid residues) contain at least one N-terminal acyl or biotinyl group, modified peptide bond and/or aminoacid residue modified at the alpha -carbon. Pseudopeptide or derivatized peptide compounds of formula (X 0) x0-(X 1) x1-(X 2) x2-(X 3) x3-(X 4) x4-(X 5) x5-(X 6) x6-(X 7) x7-(X 8) x8(I) (preferably having 4-8 (especially 5-7, particularly 6) aminoacid residues) and their salts are new. x1 - x9 : 0 or 1; X 0Q-Y-CO- or HY-CO-; Q : biotin residue of formula (a); Y : 1-24C linear, branched or cyclic alkylene; X 1, X 3natural or synthetic aminoacid having at least one hydroxy function in the side-chain; X 2natural or synthetic aminoacid having an alkyl side-chain; X 4natural or synthetic aminoacid having an aromatic side-chain; X 5lysine, arginine, histidine, aspartic acid, asparagine, glutamic acid or glutamine; X 6tyrosine, phenylalanine, leucine, isoleucine, alanine, p-benzoyl-phenylalanine or lysine; X 7glycine, alanine, leucine, valine, asparagine or arginine; X 8proline, valine, isoleucine or aspartic acid; X 9serine, alanine, lysine, arginine or tryptophan; bond between two successive aminoacids : peptide bond (CONH) or a pseudopeptide bond selected from CO-O, CO-S, CO-CH 2, CON(Me), NHCO, CH=CH, CH 2-CH 2, CH 2-S, CH 2-O, CS-NH, CH 2-NH or CO-CH 2NH; all aminoacid residues in X 1- X 9are optionally modified by replacement of the alpha -carbon structure of formula -CHR- by -C(=CH-R 1)-, -C(R)(R 2)- or -N(R)-; R, CH-R 1aminoacid side-chain; R 21-6C alkyl; or C(R)(R 2) : ring; provided that (i) x 0= 1, (ii) a pseudopeptide bond is present or (ii) an aminoacid residue carries one of the above alpha -C modifications. An independent claim is also included for new molecules (I') comprising (I) coupled at the C- and/or N-terminal with another molecule for improving the bioavailability. [Image] ACTIVITY : Cytostatic; Immunosuppressive; Anti-HIV; Antiinflammatory; Cardiant; Cerebroprotective; Vasotropic; Vulnerary; Neuroprotective; Nootropic; Antiparkinsonian; Dermatological. MECHANISM OF ACTION : Proteasome modulator; proteasome active and/or regulatory site ligand. In particular (I) bond to the CT-L (chymotrypsin-like) active and/or regulatory sites of proteasome. Biot-Ava-TVT-Bpa-KF (Ia) had IC 5032 mu M in binding assays for the CT-L (chymotrypsin-like) active and/or regulatory sites of proteasome.</p> |