Jd. Fisk et al., Control of hairpin formation via proline configuration in parallel beta-sheet model systems, J AM CHEM S, 122(23), 2000, pp. 5443-5447
The simplest strategy for creation of parallel beta-sheet model systems is
to link adjacent peptide strands via their N-termini or via their C-termini
. This connectivity requires unnatural linking segments. We describe dipept
ide mimics that can serve as N-to-N or C-to-C: linkers, and we demonstrate
their efficacy by conformational analysis of tetrapeptide analogues in chlo
roform. The tetrapeptide analogues can adopt strand-loop-strand ("hairpin")
conformations in which the residues at each end, L-valine and L-leucine, e
ngage in parallel sheet hydrogen bonding interactions. Our linkers contain
proline residues, to impart a preferred local twist. We show that linkers c
ontaining D-proline promote parallel sheet interactions between the strand
L-residues, while linkers containing L-proline do not promote parallel shee
t interactions. The preference for one linker twist is presumably related t
o the right-handed twist displayed by strands in protein beta-sheets (paral
lel and antiparallel); analogous linker twist preferences have been observe
d in antiparallel beta-sheet model systems.