Solid-phase synthesis and cyclization of a large branched peptide from IgGFc with affinity for Fc gamma RI

A solid phase approach has been used to synthesize a large branched disulph ide peptide from IgG Fc, Ac-F-C*-A-K-V-N-N-K-D-L-P-A-P-I-E-K(Ac-E-L-G-G-G-P -S-V-F)-C*-I-NH2. This peptide combines the lower hinge region of IgG and a proximal beta-hairpin loop, both implicated in binding to Fc gamma RI. Sol id phase Tl(tfa)(3) cyclization of the linear branched peptide resulted in a poor yield of cyclic hinge-loop peptide (11%) most likely due to steric h indrance caused by the branch. However, if addition of the branch was prece ded by solid phase Tl(tfa)(3) cyclization of the loop, the yield was excell ent at 75%, Cyclic hinge-loop peptide was active in displacing IgG2a from F c gamma RI expressed on monocyte cell Lines with an IC50 of 40 mu M, wherea s the linear form of this peptide was inactive. The Fc hinge-loop peptide d emonstrates the potential for a non-mAb high affinity, immunomodulatory lig and for Fc gamma RI. Copyright (C) 1999 European Peptide Society and John W iley & Sons, Ltd.