Konformationsstudien an Partialsequenzen von ACTH und Analogen. Theoretische Vorhersagen und CD-Untersuchungen an Polyethylenglykol-gebundenen Oligopeptiden / Conformational Studies on Partial Sequences of ACTH and Analogues. Theoretical Predictions and CD Investigations of Polyethylene glycol)-bound Oligopeptides

Abstract

<jats:title>Abstract</jats:title><jats:p> Conformational studies on synthetic segments)* of ACTH using circular dichroism (CD) are described. The segments [Val<jats:sup>4</jats:sup>]-ACTH (1-10) = I, [Pro<jats:sup>1</jats:sup>, Ala<jats:sup>2</jats:sup>, Ala<jats:sup>3</jats:sup>, Val<jats:sup>4</jats:sup>]-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 H<jats:sub>2</jats:sub>O. 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.</jats:p>

Conformational studies of poly(oxyethylene)-bound peptides and protein sequences

“…40,43 The influence of the N-terminal amino acid on the overall conformation of the peptide can be observed from the CD analysis of the POE-bound, modified ACTH(l-lO) sequence, [Pro\Ala2,Ala3,Val4]ACTH(l-10). 60 No transition to ß structure was observed on changing the solvent, indicating a helix-inducing effect of Pro at the N-terminus of a peptide. However, a destabilization of the helical structures was observed in aqueous solution and the ellipticity values were also significantly reduced compared to the organic medium.…”