We
report a simple reductive amination protocol to ligate two peptides,
while simultaneously installing a β-turn mimic at the ligation
junction. This strategy uses commercially available materials, mild
chemical conditions, and a chemoselective ligation reaction of unprotected
peptide substrates accessed through standard solid phase methods.
This system was implemented in a designed β-hairpin system,
and biophysical analysis demonstrates effective mimicry of the β-turn.
The
(+) and (−) enantiomers of a new turn-inducing cyclopropyl
dipeptide mimic have been synthesized and evaluated. The mimic derives
its turn-inducing capabilities solely from the cyclopropyl group and
without the conformational biasing that would be provided by side-chain
substituents. The mimic and peptide-mimic hybrids prepared from it
have been studied using a combination of spectroscopic techniques
(NMR, IR, and CD). The dipeptide mimic itself displays intramolecular
hydrogen bonding in organic solvents, which differs from that observed
in natural peptide turns. In contrast, more elaborate peptide-mimic
hybrids exhibit hydrogen bonding characteristics that vary with solvent
but are consistent with structures found in the tetrapeptide portion
(i → i + 3) of a native β-turn.
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