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Solid‐phase synthesis and cyclization of a large branched peptide from IgG Fc with affinity for FcγRI
Author(s) -
Sheridan Joseph M.,
Hayes Gillian M.,
Austen Brian M.
Publication year - 1999
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/(sici)1099-1387(199912)5:12<555::aid-psc220>3.0.co;2-g
Subject(s) - peptide , chemistry , steric effects , cyclic peptide , stereochemistry , yield (engineering) , solid phase synthesis , ligand (biochemistry) , receptor , biochemistry , materials science , metallurgy
Abstract A solid phase approach has been used to synthesize a large branched disulphide peptide from IgG Fc, Ac‐F‐C*‐A‐K‐V‐N‐N‐K‐D‐L‐P‐A‐P‐I‐E‐K(Ac‐E‐L‐L‐G‐G‐P‐S‐V‐F)‐C*‐I‐NH 2 . This peptide combines the lower hinge region of IgG and a proximal β‐hairpin loop, both implicated in binding to FcγRI. Solid 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 hindrance caused by the branch. However, if addition of the branch was preceded by solid phase Tl(tfa) 3 cyclization of the loop, the yield was excellent at 75%. Cyclic hinge–loop peptide was active in displacing IgG2a from FcγRI expressed on monocyte cell lines with an IC 50 of 40 μ M , whereas the linear form of this peptide was inactive. The Fc hinge–loop peptide demonstrates the potential for a non‐mAb high affinity, immunomodulatory ligand for FcγRI. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.