We are interested in the chemistry and biology of steroids. My laboratory specializes in natural products chemistry as it relates to the synthesis of steroids and steroid analogues. The compounds prepared in the laboratory are then studied in laboratories of colleagues throughout the university, and elsewhere, who share with us a common interest in the biological actions of steroids. Currently our efforts are focused in four main areas: 1) neuroactive steroids; 2) neuroprotective steroids; 3) cholesterol and bile steroid homeostasis; and 4) steroid effects on the physical properties of model membranes. Neuroactive steroids affect the functioning of ion-channels involved in synaptic transmission in the central nervous systems. Some of these neuroactive steroids are potent anesthetics and the chemistry carried out on this project is designed either to provide mechanistic information on how steroids cause anesthesia or to provide new structure—activity data for the development of new anesthetic steroids. Neuroprotective steroids are steroids that prevent or reduce neurodegeneration. We are interested in steroids that prevent neuronal cell death caused by oxidative damage. The complex process whereby cells regulate the production and distribution of cholesterol and bile steroids in cells is incompletely understood. Steroids prepared in this project area are ed for their ability to provide a better understanding of this complex regulation. Finally, we are interested in developing anew method to distinguish between the membrane and receptor-mediated effects of steroids. The method involves the synthesis of steroid enantiomers and biophysical and biochemical studies of their properties.
Research Publications
Jiang X, Manion BD, Benz A, Rath NP, et al. Neurosteroid analogues. 9. Conformationally constrained pregnanes: structure-activity studies of 13,24-cyclo-19,21-dinorcholane analogues of the GABA modulatory and anesthetic steroids (3a,5a) and (3a,5b)-3-hydroxypregnan-20-one. J Med Chem 2003 46:5334-5348. Full Article >
Darbandi-Tonkabon R, Manion BD, Hasting WR, Craigen WJ,et al. Neuroactive steroid interactions with voltage-dependent anion channels: lack of relationship to GABAA receptor modulation and anesthesia. J Pharmacol Exp Ther 2004 308:502-511. Full Article >
Mennerick S, He Y, Jiang X, Manion BD, Wang M, et al. ive antagonism of 5a-reduced neurosteroid effects at GABAA receptors. MOL PHARMACOL 2004 65:1191-1197 Full Article >
Shu H-J, Eisenman LN, Jinadasa D, Covey DF, et al. Slow actions of neuroactive steroids at GABAA receptors. J NEUROSCI 2004 24:6667-6675. Full Article >
Todorovic SM, Pathirathna S, Brimelow BC, Jagodic MM, et al. 5b-reduced neuroactive steroids are novel voltage-dependent blockers of T-type Ca2++ channels in rat sensory neurons in vitro and potent peripheral analgesics in vivo. MOL PHARMACOL 2004 66:1223-1235. Full Article >
Simpkins JW, Yang S-H, Liu R, Perez E, et al. Estrogen-like compounds for ischemic neuroprotection. STROKE 2004 35(Suppl. 1): 2648-2651. Full Article >
Contact Info
Douglas Covey, Ph.D.
Office Location: 355 McDonnell Science Bldg.
Office Phone: 314-362-1726
Campus Box: 8103
Fax: 314-362-7058
dcovey@wustl.edu
http://molecool.wustl.edu/covey.htm
