Extended conformations in alanine peptides

Spectroscopic evidence for the presence of local order in unfolded proteins, including polyproline I delta (PII) structure, now appears incontrovertible. The data supporting this order relies on analysis of short chain peptides. The dimensions of unfolded chains nevertheless conform to random coils. We have re-examined the dimensional properties of short chains using paramagnetic proton spin relaxation measurements to evaluate intermediate range distances (r) within alanine peptides linked to short proline arms.(1) Two peptides were employed in our studies, OO-T super(*)-PPPA super(*)PPPA super(*)-OO and OO-T super(*)-PPPAAAA super(*)-OO, where O is Ornithine, T super(*) is Toac (2,2,6,6-Tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), A super(*) is 15N labelled alanine. Mesostate based Monte-Carlo sampling calculations (2) were carried out to interpret the relaxation data. The conclusion of the study is that over 90% occupation of extended conformations, i.e. PI delta and b mesostates, is required to reproduce the experimentally observed distance averaging. Compact structures including aR, aL and turns are clearly present but are not dominant in the conformational ensemble. Analysis of the conformation of other side chains will be presented. (1) Chen, K et al. Ang. Chem. Int. Ed. 2007 46, 9036. (2) Gong, H, Fleming, PH, Rose, GD. Proc. Natl. Acad. Sci. USA 2005, 102, 16227.