Vol. 143. No. 3, 1987 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS March 30, 1987 Pages 1005-1011 RESOLUTION OF CONFORMATIONAL EQUILIBRIA IN LINEAR PEPTIDES BY CIRCULAR DICHROISM IN CRYOGENIC SOLVENTS G. Siligardia, A.F. Drakeb, P. Mascagnia, P. Neric, L. Lossi', N. Niccolai', and W.A. Gibbonsa aDept. of Pharmaceutical Chemistry, School of Pharmacy, London, UK bDept. of Chemistry, Birkbeck College, London, UK 'Universita' di Siena and C.R.I.S.M.A. Siena, Italy Received February 13, 1987 lhe circular dichroism spectra of the synthetic peptide antigen, 209-222 of the surface glycoprotein of the rabies virus were recorded as a function of solvent composition and over tile temperature range of +6O"C to -135°C; 8-IIC and p-11 reverse turn conformations were found to exist in TFE/H20 (3:l) at room temperature and in ethanediollH20 (2:l) below -110°C respectively. Evidence, from comparison of observed and calculated spectra, is given to support the existence of a conformational equilibrium between a B-11 and a B-III reverse turn. These data can serve as a basis for synthetic vaccine development and understanding the nature of polypeptide chain folding. ; 1987 Academic Press, Inc. The acetylcholine receptor not only binds its endogenous ligands but is the target for neurotoxins such as cl-bungarotoxin (I), the rabies virus peplomer glycoprotein (2) and autoantibodies that mediate the autoimmune disease myasthenia gravis (3). The above facts led to the hypothesis that the rabies glycoprotein and the neurotoxins could possess sequence and possibly conformational homology and that these homologous regions could be commonly recognized by the acetylcholine receptor. The sequences 208-223 of the glycoprotein and 30-45 of the snake neurotoxins which are thought to be involved in the binding to the cholinergic receptor have been shown to exhibit extensive sequence homology (4). Since the three dimensional structure of some neurotoxins have been established (5) it was important to investigate whether the 203-223 rabies peptide possessed conformational homology with the corresponding 30-45 sequence from the neurotoxin. Accordingly the 209-222 sequence (DIFTNSRGKRASKG called RP14) was synthesised and its conformation studied as 0006-291X/87 $1.50 1005 Copyright 0 1987 by Academic Press. Inc. All rights of reproduction in any form reserved.