DESIGN OF MHC CLASS-II (DR4) LIGANDS USING CONFORMATIONALLY RESTRICTED IMINO ACIDS AT P3 AND P5

Authors
HANSON GJ VULETICH JL BEDELL LJ BONO CP HOWARD SC WELPLY JK WOULFE SL ZACHEIS ML
Citation
Gj. Hanson et al., DESIGN OF MHC CLASS-II (DR4) LIGANDS USING CONFORMATIONALLY RESTRICTED IMINO ACIDS AT P3 AND P5, Bioorganic & medicinal chemistry letters, 6(16), 1996, pp. 1931-1936
Citations number
10
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
6
Issue
16
Year of publication
1996
Pages
1931 - 1936
Database
ISI
SICI code
0960-894X(1996)6:16<1931:DOMC(L>2.0.ZU;2-A
Abstract
High potency synthetic ligands were designed for rheumatoid arthritis linked Class II MHC, DR4 Dw4. The design strategy utilized isosteric r eplacements at the p1 and p7 positions and conformational restriction with imino acids pipecolic acid (Pec) and proline at the solvent expos ed residues p3 and p5. In particular, SC-67655, (S)-CBA-Val-Pec-Asp-Pr o-Thr-NH-n-Pr (IC50 = 50 nM) is a potent and stable pentapeptide DR4 l igand. Copyright (C) 1996 Elsevier Science Ltd