12/10-Helical β‑Peptide with Dynamic Folding Propensity: Coexistence of Right- and Left-Handed Helices in an Enantiomeric Foldamer

• Published in: Journal of the American Chemical Society 2016-10, Vol.138 (40), p.13390-13395
• Main Authors: Shin, Seonho, Lee, Mihye, Guzei, Ilia A, Kang, Young Kee, Choi, Soo Hyuk
• Format: Article
• Language: English
• Subjects: Crystallography, X-Ray; Cyclohexanes - chemistry; Models, Molecular; Oligopeptides - chemistry; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Folding; Protein Multimerization; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.6b08235

We present the first examples of atomic-resolution crystal data for the β-peptide 12/10-helix from oligomers of cis-2-aminocyclohexane carboxylic acid (cis-ACHC) with alternating chirality. The local conformations of two enantiomeric cis-ACHC dimer units suggested that a chiral β-peptide may adopt both right-handed and left-handed helical conformations in solution. To probe the conformational behavior of 12/10-helical β-peptides, the two reference helices with a single handedness were synthesized with a more rigidified cis-ACHC derivative. Comparison with these reference helices at low temperature revealed that a chiral cis-ACHC oligomer with alternating chirality indeed displays 12/10-helical conformations with both handedness that equilibrate rapidly in solution. This is a very rare example of chiral oligomers with helix inversion ability. The 12/10-helical backbone should be a valuable addition to potential scaffolds for applications involving helices with dynamic folding propensity.