| Abstract
| - The nonapeptide fragment of the HLA−DR molecule, located in the exposed loop of the β chain (164−172) andhaving the sequence VPRSGEVYT, suppresses the immune response. On the basis of the three-dimensional structureof the HLA−DR superdimer, we designed new dimeric analogs in which the VPRSGEVYT peptides are linkedthrough their N-termini by poly(ethylene glycol) linkers of different lengths and are able to mimic the dimericnature of the immunosuppressive fragments of HLA class II molecules. The analogs were synthesized usingstandard solid-phase peptide synthesis protocols. The dimerization was achieved by cross-linking the N-terminalpositions of the peptides, attached to an MBHA resin, with α,ω-bis(acetic acid) poly(ethylene glycol), activatedby esterification with pentafluorophenol. Our results demonstrate that the amino-terminal dimerization of thepeptide results in enhanced immunosuppressive activity and that the potency of the conjugates depends on thelength of the poly(ethylene glycol) linker. MS/MS analysis of the obtained dimeric peptides is also presented.
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