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N-1 and N-2 positional effects in the propagation of 310-type fold in the helical model peptide Boc– (D)Glu– Pro– Ala– Lys– Ala– Leu– Ala– OMe

✍ Scribed by S. Beri; Sudha Srivastava; M. Dhanasekaran; Ratna S. Phadke; S. Durani


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
119 KB
Volume
38
Category
Article
ISSN
0749-1581

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✦ Synopsis


The N-1 Ala 2 and N-2 Gly 3 positional amino acids in the type II 0 turn templated 3 10 helix Boc-(D)Glu 1 -Ala 2 -Gly 3 -Lys 4 -NHMe (1) and Boc-(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 -type helix endlocked by Boc-(D)Glu 1 , with a stronger Lys ! Glu salt bridge but a comparatively weaker helical domain, more susceptible to solvent-mediated disordering. The relatively constrained residues of higher N cap and internal positional helix propensities are thus shown actually to weaken the helical domain in our model, because its helix-templating segment distorts and thus its template-assisted propagation as a 3 10 helix is compromised. The dependence of geometry and stability of an ordered helical structure on effects in its folding initiation and templateassisted propagation are thus shown to be captured in a helical model peptide of unusual structural simplicity.