SynopsisThe conformation of polyethylene glycol-bound peptides, synthesized by the liquidphase method, was investigated. This marcromolecular C-terminal protecting group is transparent in the visible and the ultraviolet range to 190 nm and solubilizes peptides in many different solvents. The CD spectra of the polymer-bound myoglobin sequence 66-73 and of the biologically active undecapeptide "substance P" were measured in each step of the synthesis. In both examples the formation of a secondary structure during the growth of the peptide chain was found.In the hydrophobic octapeptide containing the myoglobin sequence 66-73, the influence of either the blocked or the free N-terminal amino group on the conformation was observed. The blocked octapeptide in trifluoroethanol showed a higher degree of a-helix contribution than in its free state.The conformation of the polyethylene glycol-bound nona-and decaalanine in trifluoroethanol and water was determined. The peptide with a free amino end group has /3-conformation in trifluoroethanol as well as in water. The corresponding N-Boc-protected derivatives show helical structure. The amino end group has a decisive influence on the formation of /%structure.The method of CD investigation of polymer-bound peptide sequences during the peptide synthesis in solution enables one to determine the influence of protecting groups and the chain end of a peptide on its conformation. It is also possible to study the relationship between the secondary structure, the chain length, and the kinetic of the coupling reaction in different solvents. Since the crystallization method for the liquid-phase peptide synthesis allows one to synthesize peptides in very short fime, a new method of studying peptide conformations is opened.

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Abstract Conformational studies on synthetic segments)* of ACTH using circular dichroism (CD) are described. The segments [Val4]-ACTH (1-10) = I, [Pro1, Ala2, Ala3, Val4]-ACTH (1-10) = II and ACTH (11-23) = III have been synthesized according to the Liquid-Phase-Method with polyethylene glycol (PEG) as solubilizing C-terminal protecting group. The peptide PEG esters were studied in water and 2,2,2-trifluoroethanol (TFE) and the dependence of chain length, side chain protection and solvent upon the conformation has been evaluated. From these measurements, I shows partially helical structure in TFE and β-conformation in H2O. The modified 10-peptide II with strong helix formers at the N-terminus shows substantial amounts of helical structure in TFE and in water. A significant increase in helical structure is observed by adding the Pro residue to the N-terminus. The CD spectra of the 13-peptide III ist also typical for partially helical structure, however other types of ordered conformations cannot be excluded. The experimental data are compared with the results from calculations of the secondary structure deduced from the empirical prediction scheme of Chou and Fasman and the more elaborated statistical mechanical treatment of peptide conformations proposed by Tanaka and Scheraga. The agreement between experimental data and theoretical prediction is reason-able for I and II, whereas III is expected to adopt extended conformations beside unordered forms. The experimentally found unique behaviour of Prolin was rationalized by the asymmetric helix nucleation feature of this residue. A model for the most probable conformation of ACTH is proposed and a critical evaluation of the predictive schemes is given.