Conformational behavior of beta-proline oligomers.
Conformations of the monomer, dimer, and hexamer of beta-proline ((S) pyrrolidine-3-carboxylic acid) were determined using ab initio molecular orbital calculations at the RHF/6-31G level of theory. The calculated minima are in good agreement with experimental data for the system and imply that the conformations could be controlled through chemical modification at Calpha, Cgamma, or Cdelta. The monomer and dimer are small and flexible with many low-energy minima. In the hexamer, two forms of regular secondary structure are preferred: left-handed helices with cis-peptide bonds and right-handed helices with trans-peptide bonds. This is similar to the behavior of alpha-proline helices, except that the relationship between the peptide rotamer and the handedness of the helix is reversed. Therefore, helices of the enantiomer of beta-proline ((R)-pyrrolidine-3-carboxylic acid) should exhibit the same behavior as alpha-proline helices. Through understanding the conformational behavior of beta-proline in various environments, it may be possible to use these protein mimics to inhibit various protein-protein recognition events. To estimate these effects, SCRF energies for the conformers were determined in dielectrics corresponding to water, methanol, and chloroform. It appears that the cis helices are more favorably solvated than the trans helices, but the cause is not clear.
Sandvoss
Leah M
LM
Department of Medicinal Chemistry, College of Pharmacy, 428 Church St., Ann Arbor, Michigan 48109-1065, USA.
Carlson
Heather A
HA
D004151:Dipeptides / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013499:Surface Properties; D013816:Thermodynamics
D004151:Dipeptides; D009842:Oligopeptides; D010455:Peptides; C011083:polyproline; D011392:Proline