1620146-28-2Relevant articles and documents
Synthesis and β-sheet propensity of constrained N-amino peptides
Sarnowski, Matthew P.,Pedretty, Kyle P.,Giddings, Nicole,Woodcock, H. Lee,Del Valle, Juan R.
supporting information, p. 1162 - 1166 (2018/03/09)
The stabilization of β-sheet secondary structure through peptide backbone modification represents an attractive approach to protein mimicry. Here, we present strategies toward stable β-hairpin folds based on peptide strand N-amination. Novel pyrazolidinone and tetrahydropyridazinone dipeptide constraints were introduced via on-resin Mitsunobu cyclization between α-hydrazino acid residues and a serine or homoserine side chain. Acyclic and cyclic N-amino peptide building blocks were then evaluated for their effect on β-hairpin stability in water using a GB1-derived model system. Our results demonstrate the strong β-sheet stabilizing effect of the peptide N-amino substituent, and provide useful insights into the impact of covalent dipeptide constraint on β-sheet folding.
