δ-Azaproline and Its Oxidized Variants.

Peptides featuring backbone N-amino substituents exhibit unique conformational properties owing to additional electrostatic, hydrogen-bonding, and steric interactions. Here, we describe the synthesis and conformational analysis of three δ-azaproline derivatives as potential proline surrogates. Our studies demonstrate stereoelectronic tuning of heterocyclic ring pucker, / amide propensity, and amide isomerization barriers within a series of oxidation state variants.

Synthesis and β-sheet propensity of constrained N-amino peptides.

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.