Conformational preferences and cis-trans isomerization of L-3,4-dehydroproline residue.
The conformational study of N-acetyl-N'-methylamide of L-3,4-dehydroproline (Ac-Dhp-NHMe, the Dhp dipeptide) is carried out using hybrid density functional methods with the self-consistent reaction field method in the gas phase and in solution (chloroform and water). The incorporation of a double bond between C(beta) and C(gamma) into the prolyl ring results in the puckering, backbone population, and barriers to prolyl cis-trans isomerization different from those of the Pro dipeptide. For local minima of the Dhp dipeptide in the gas phase and in water, the C(beta)-C(gamma) bonds become shorter by approximately 0.2 A and the bond angles C(alpha)-C(beta)-C(gamma) and C(beta)-C(gamma)-C(delta) are widened by approximately 8 degrees than those of the Pro dipeptide, and the puckering amplitude is computed to be 0.01-0.07 A, indicating that the 3,4-dehydroprolyl ring is quite less puckered. However, polyproline-like conformations become preferred and the relative stability of the conformation tC with a C(7) intramolecular hydrogen bond decreases as the solvent polarity increases, as found for the Pro dipeptide. The barriers to cis-trans isomerization of the Ac-Dhp peptide bond increase with the increase of solvent polarity and the isomerization is likely to proceed through the clockwise rotation in water, as found for the prolyl peptide bond. The hydrogen bond between the prolyl nitrogen and the following amide N-H group seems to contribute in stabilizing the transition state structures.
Kang
Young Kee
YK
Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea. ykkang@chungbuk.ac.kr
Park
Hae Sook
HS
D000818:Animals; D002645:Chickens; D007536:Isomerism; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D011487:Protein Conformation; D013816:Thermodynamics
D010455:Peptides; C002195:3,4-dehydroproline; D011392:Proline