Bending Rigid Molecular Rods: Formation of Oligoproline Macrocycles

• Published in: Chemistry : a European journal Vol. 18; no. 49; pp. 15612 - 15617
• Main Authors: Scully, Conor C. G., Rai, Vishal, Poda, Gennadiy, Zaretsky, Serge, Burns, Darcy C., Houliston, R. Scott, Lou, Tiantong, Yudin, Andrei K.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 03.12.2012; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Attraction; Bending; Bends; Chemistry; Chemistry, Multidisciplinary; Circular Dichroism; Cyclization; Dichroism; electrostatic interactions; Formations; macrocycles; Macrocyclic compounds; Macrocyclic Compounds - chemistry; Molecular structure; Oligopeptides - chemistry; Organosilicon Compounds - chemistry; Peptides; Peptides - chemistry; Physical Sciences; polyproline; Science & Technology; Stitching; CIRCULAR-DICHROISM SPECTRUM; STABILITY; POLYPROLINE-II HELIX; COMPLEXES; peptides; circular dichroism; polyproline; PEPTIDOMIMETICS; macrocycles; CYCLIC POLYETHERS; POLY-L-PROLINE; BIOLOGICAL-ACTIVITY; CONFORMATIONAL-ANALYSIS; electrostatic interactions
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201203266

Bent but not broken: Cyclic oligoprolines are accessed in a reaction that effectively bends rigid oligoproline peptides (see scheme; TBDMS=tert‐butyldimethylsilyl). The stitching is accomplished during macrocyclization enabled by aziridine aldehydes and isocyanides. Molecular modeling studies suggest that electrostatic attraction between the termini of the linear peptide is pivotal for macrocyclization. The macrocycles were studied by circular dichroism with a polyproline II structure being observed in larger macrocycles.