The techniques of computer-assisted molecular modeling have been applied to a variety of problems in the Laboratory of Medicinal Chemistry. Pharmacophore detection and analysis is a standard task, as is analysis of receptor sites and discovery of new lead compounds having known pharmacophores. Modeling Studies: Molecular models of a large number of compounds from the NCI database have been compared to the x-ray structures and the differences identified and rationalized. Protein Kinase C: Compounds that possess the correct pharmacophore and which can activate protein kinase C continue to be discovered. Some particularly potent phorbol competitors have been identified. Modeling of the structure of the zinc finger regions of protein kinase C has begun. Tyrosine Protein Kinase: A set of structural requirements for the inhibition of tyrosine protein kinase has been delineated and used in searches of the 3D database to identify several new lead compounds. Reverse Transcriptase Inhibitors: A large series of fluorine-containing dideoxynucleosides has been modeled and some of the structural requirements for RT inhibition have been identified. Three-Dimensional Database: Conversion of the NCI database from 2-D to 3-D coordinates is now well advanced. A new structure building program, CHEM-X, has been acquired and installed and has been found to give superior results to those obtained using CONCORD.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CM006194-04
Application #
3838043
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Division of Cancer Treatment
Department
Type
DUNS #
City
State
Country
United States
Zip Code