V. Theodorou et al., Design, synthesis, and conformational study of biologically active photolabeled analogues of the main immunogenic region of the acetylcholine receptor, BIOPOLYMERS, 56(1), 2000, pp. 37-46
Photoaffinity labeling is a powerful tool for the characterization of the m
olecular basis of ligand binding to acceptor molecules, which provides impo
rtant insights for mapping the bimolecular interfaces. The autoimmune disea
se myasthenia gravis is caused by autoantibodies against the acetylcholine
receptor (AChR). The majority, of the anti-AChR antibodies bind to the "mai
n immunogenic region" (MIR) of the AChR. To identify, the contact points be
tween the complementarity determining regions of the anti-MIR antibodies th
at recognize the MIR contact sites of the AChR, we present here three photo
reactive dodecapeptide MIR analogues containing the photolabel p-benzoyl-L-
phenylalanine (Bpa) moiety, either in position 1 or 11. The structure of th
e produced 12-mers was analyzed using two-dimensional H-1-NMR spectroscopy,
whereas their binding to anti-MIR monoclonal antibodies (mAbs) was determi
ned by immunochemical assays. In all cases the modifications resulted in co
nservation of the beta -turn conformation of the N-terminus, which has been
proved essential for antibody recognition and increased anti-MIR binding r
elative to the MIR decapeptide. (C) 2001 John Wiley & Sons, Inc.