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Design, synthesis, and conformational study of biologically active photolabeled analogues of the main immunogenic region of the acetylcholine receptor
Author(s) -
Theodorou Vassiliki,
Tsikaris Vassilios,
SakarellosDaitsiotis Maria,
Avramopoulou Vassiliki,
Kostelidou Kalliopi,
Tzartos Socrates J.,
Sakarellos Constantinos
Publication year - 2000
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/1097-0282(2000)56:1<37::aid-bip1041>3.0.co;2-x
Subject(s) - chemistry , acetylcholine receptor , moiety , stereochemistry , monoclonal antibody , myasthenia gravis , complementarity determining region , antibody , photoaffinity labeling , receptor , biochemistry , biophysics , peptide sequence , medicine , gene , immunology , biology
Photoaffinity labeling is a powerful tool for the characterization of the molecular basis of ligand binding to acceptor molecules, which provides important insights for mapping the bimolecular interfaces. The autoimmune disease myasthenia gravis is caused by autoantibodies against the acetylcholine receptor (AChR). The majority of the anti‐AChR antibodies bind to the “main immunogenic region” (MIR) of the AChR. To identify the contact points between the complementarity determining regions of the anti‐MIR antibodies that recognize the MIR contact sites of the AChR, we present here three photoreactive dodecapeptide MIR analogues containing the photolabel p‐benzoyl‐ L ‐phenylalanine (Bpa) moiety, either in position 1 or 11. The structure of the produced 12‐mers was analyzed using two‐dimensional 1 H‐NMR spectroscopy, whereas their binding to anti‐MIR monoclonal antibodies (mAbs) was determined by immunochemical assays. In all cases the modifications resulted in conservation of the β‐turn conformation of the N‐terminus, which has been proved essential for antibody recognition and increased anti‐MIR binding relative to the MIR decapeptide. © 2001 John Wiley & Sons, Inc. Biopolymers 56: 37–46, 2001