N-1 and N-2 positional effects in the propagation of 3(10)-type fold in the helical model peptide Boc-(D)Glu-Pro-Ala-Lys-Ala-Leu-Ala-OMe

The N-1 (Ala(2)) and N-2 (Gly(3)) positional amino acids in the type II' tu rn templated 3(10) helix Boc-(D)Glu(1)-Ala(2)-Gly(3)-Lys(4)-NHMe (1) and Bo c-(D)Glu(1)-Ala(2)-Gly(3)-Lys(4)-Ala(5)-Leu(6)-OMe (3) are substituted with Pro(2) and Ala(3) to obtain its variants Boc-(D)Glu(1)-Pro(2)-Ala(3)-Lys(4 )-NHMe (2) and Boc-(D)Glu(1)-Pro(2)-Ala(3)-Lys(4)-Ala(5)-Leu(6)-Ala(7)-OMe (4). According to NMR evidence, the resultant peptide (4) is also a 3(10)-t ype helix endlocked by Boc-(D)Glu(1), with a stronger Lys --> Glu salt brid ge but a comparatively weaker helical domain, more susceptible to solvent-m ediated disordering. The relatively constrained residues of higher N cap an d internal positional helix propensities are thus shown actually to weaken the helical domain in our model, because its helix-templating segment disto rts and thus its template-assisted propagation as a 310 helix is compromise d. The dependence of geometry and stability of an ordered helical structure on effects in its folding initiation and template-assisted propagation are thus shown to be captured in a helical model peptide of unusual structural simplicity. Copyright (C) 2000 John Wiley & Sons, Ltd.