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Cyclodimerization of immunosuppressive fragment of HLA‐DR molecule. Design, synthesis and ESI‐MS/MS analysis
Author(s) -
Biernat Monika,
Cydzik Marzena,
Stefanowicz Piotr,
Kluczyk Alicja,
Artym Jolanta,
Zimecki Michał,
Szewczuk Zbigniew
Publication year - 2016
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2898
Subject(s) - peptide , chemistry , ethylene glycol , peptide synthesis , molecule , fragmentation (computing) , stereochemistry , peptide sequence , solid phase synthesis , combinatorial chemistry , biochemistry , organic chemistry , biology , gene , ecology
The nonapeptide fragment of the HLA‐DR molecule, located in the exposed loop of the alpha‐chain (164–172), having the VPRSGEVYT sequence, suppresses the immune response. Based on the three‐dimensional structure of the HLA‐DR superdimer, we designed a new cyclodimeric analog in which the two parallel peptide chains of VPRSGEVYT sequence are linked through their C‐termini by spacer of (Gly 5 ) 2 ‐Lys‐NH 2 and the N‐termini are also linked by poly(ethylene glycol). The (VPRSGEVYTG 5 ) 2 K‐resin analog was synthesized using solid‐phase peptide synthesis protocols. The cyclization was achieved by cross‐linking the N‐terminal positions of the dimeric peptide, attached to a MBHA resin, with alpha, omega‐bis (acetic acid) poly(ethylene glycol), activated by esterification with pentafluorophenol. Our results demonstrate that the cyclodimerization of VPRSGEVYT results in enhanced immunosuppressive activity of the peptide. Mass spectrometry fragmentation analysis of the obtained cyclodimeric peptide is also presented. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.