Dr. Raj Rajnarayanan, Associate Professor of Chemistry, has established a medicinal chemistry and drug discovery facility to design synthesis and perform basic pre-clinical biological testing of anti-cancer agents. His lab focuses on the discovery of conformation sensing small molecules as novel anti-cancer agents against human estrogen receptors.
The major accomplishments include the generation of moderate resolution structures of calcium calmodulin and calmodulin interacting peptide complexes using chemical crosslinking coupled with mass spectroscopy and the development of fluorescent polarization based assay to analyze protein-peptide interactions. To our knowledge, these provided the first example of structure-assisted proteomics based moderate resolution models of CaBP-interacting peptide complexes at the interface crucial for protein-protein interactions. The identified interface peptides and the distance constraints between residues are useful in defining the network of protein interactions and the protein folding of the assembly. These protein interfaces are potential targets for structure guided drug development. This interaction was confirmed with FP based interaction analyses of CaM binding to a fluorescently labeled peptide with or without CaM antagonist (W7) at low and high PCa conditions. Another FP assay was used to probe binding affinity of selected peptides against ER-ligand complexes. The peptide EDGGSLFERVWLRELG binds to ER-estradiol complex specifically however changing a few residues alter this recognition.
These observations strengthen the overall hypothesis of the project and provide valuable insight into the hormonal control of protein expression/function and structural basis for drug discovery. Dr. Rajnarayanan collaborates with Dr. Cholanayakanahalli R. Vinayaka of Georgetown University and Dr. Pradip Biswas (Tougaloo) on the drug discovery projects, and collaborates with Dr. Hari H.P. Choly and Dr. Raphael Isokpehi at Jackson State University (JSU). Tougaloo undergraduates have been able to enhance their research by using the facilities at nearby JSU. Research in his laboratory has resulted in rigorous training of undergraduate students at the interface of biology and chemistry. Three of the recent five undergraduate researchers have been accepted to graduate programs.
Raj Rajnarayanan, Ph.D.
Associate Professor of Chemistry