Secondary structural preferences of 2,2-disubstituted pyrrolidine-4-carboxylic acid oligomers: beta-peptide foldamers that cannot form internal hydrogen bonds.
We examine a new class of beta-peptides, 2,2-disubstituted pyrrolidine-4-carboxylic acid oligomers, and show that they manifest discrete conformational preferences despite the impossibility of internal hydrogen bonding. Numerous beta-peptide families have been described that display specific secondary structural preferences, but all of the conformations characterized in detail so far have contained internal hydrogen bonds. Internal hydrogen bonding is observed within the most common secondary structures of conventional peptides as well. Identifying foldamers in which shape control is independent of hydrogen bonding is significant in two ways. At a fundamental level, foldamers in this small but growing class are interesting because their shapes are controlled by distinctive networks of noncovalent forces. At a practical level, non-hydrogen bonded foldamers may be useful in biomedical applications because the low intrinsic polarity of their backbones may promote bioavailability.
Huck
Bayard R
BR
Department of Chemistry and Graduate Program in Biophysics, University of Wisconsin, Madison, WI 53706, USA.
Fisk
John D
JD
Guzei
Ilia A
IA
Carlson
Heather A
HA
Gellman
Samuel H
SH
D002264:Carboxylic Acids / Q000737:chemistry; D002942:Circular Dichroism; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011759:Pyrrolidines / Q000737:chemistry*
D002264:Carboxylic Acids; D009842:Oligopeptides; D011759:Pyrrolidines