Synthesis and characterization of constrained cyclosporin A derivatives containing a pseudo-proline group

The chemical synthesis, conformational analysis and receptor binding studies of novel constrained cyclosporin A (CsA) analogues are described. The selective insertion of pseudo-proline (PsiPro) systems featuring different 2-C-substituents at the oxazolidine ring exerts dramatic effects upon the backbone conformation as demonstrated by NMR analysis. It is shown that the insertion of a Psi(MeMe)pro at position 5 (Thr(5)CsA) maintains binding to cyclophilin A as well as to calcineurin and shows a 5-6 cis amide bond with all remaining amide bonds trans. The elaborated synthetic routes for generating PsiPro containing Cs derivatives pave the way for extended structure-activity relationship studies aiming at the design of potential pharmacologically active compounds with a selective activity profile. (C) 2003 Elsevier Science Ltd. All rights reserved.


Published in:
Tetrahedron, 59, 28, 5241-5249
Year:
2003
ISSN:
0040-4020
Other identifiers:
Laboratories:




 Record created 2006-02-09, last modified 2018-01-27


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