Conformational study of the acetyl group and cyclohexenone in progesterone interacting with phosphatidyllipid by means of circular dichroism.
The interaction between the A-ring and the 17-acetyl groups of progesterone (PROG) and various concentrations of distearoyl-, dipalmitoyl-, dioleoyl- and diarachidoyl-L-alpha-phosphatidylcholines, and dipalmitoyl-L-alpha-phosphatidyl-DL glycerol in methanol and chloroform solutions and its preferred conformational assignments in the presence of those lipids were examined qualitatively by circular dichroism on the basis of PROG spectra in the wavelength regions of 260-400 nm. PROG did not interact with saturated distearoyl and dipalmitoyl phosphatidylcholines, but did with unsaturated dioleoyl and diarachidoyl phosphatidylcholines, and saturated dipalmitoylphosphatidylglycerol. The interacting moieties of PROG were an alpha,beta-unsaturated cyclohexenone of the A-ring for oleoyl and glycerol lipids, and the 17-acetyl group for unsaturated and glycerol lipids. The interaction with these lipids, the rotational conformations of the 17-acetyl group, and invertible conformations of the cyclohexenone of PROG were discussed on the basis of the elliptical strength of the Cotton effect and energy estimation of the preferred conformers. Oleoylphosphatidylcholine caused an increase in slightly energetically unstable conformers of the acetyl group and stable conformers of the alpha,beta-unsaturated cyclohexenone. Glycerol lipid, on the other hand, caused an increase in energetically unstable conformers of cyclohexenone, but it was similar to the effect of oleoyl lipid on the 17-acetyl group. Diarachidoyl-L-alpha-phosphatidylcholine, with eight double bonds, other hand, increased the number of energetically stable conformers of the 17-acetyl group, but had no effect on the conformation of cyclohexenone. It became apparent that the double bond of hydrocarbon moiety as well as the head group of choline and glycerol in lipids were closely related to the conformational populations of both groups of the PROG molecule. The specific effect on the conformations of the acetyl and alpha,beta-unsaturated cyclohexenone of PROG of various lipids with different substitutions in their heads or hydrocarbon moieties might in part explain the nongenomic action of the steroid.
Watanabe
S
S
Department of Pharmacology, Kawasaki Medical School, Okayama, Japan.
Saito
T
T
Ikeda
M
M
D002942:Circular Dichroism; D008968:Molecular Conformation; D010713:Phosphatidylcholines / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D013329:Structure-Activity Relationship
D010713:Phosphatidylcholines; D011374:Progesterone