Highly conformation constrained β-proline based methanopyrrolidine-5-carboxylic acids (6, MetPyr-5-acids, or MetPyr-β-amino acids) derivatives were designed, synthesized, and investigated to control peptide conformation and oligomer folding. Enhanced order of folding uniformity correlated with length of the prepared homo-oligomers as characterized by circular dichroism (CD). The octamer (34) exhibited minimal solvent effects and was stable with increasing temperature up to 80 °C. Substitutions on C6 of the 2-azabicyclo[2.1.1] hexane structure could modulate the amide cis/trans conformation.
All Science Journal Classification (ASJC) codes
- Drug Discovery
- Organic Chemistry