We are using NMR experiments (e.g., transferred nuclear Overhauser effect (trNOESY), water LOGSY, and saturation transfer difference spectroscopy) to experimentally screen for the binding activity of small molecules to:
- Develop detection reagents for Clostridial neurotoxins, anthrax proteins, and Yersinia pestis proteins, in collaboration with Rod Balhorn, (Cosman et al., 2002, Chem. Res. Toxicol. 15, 1218-1228).
- Study the interactions between the estrogen receptor protein and heterocyclic amines (food mutagens), in collaboration with Brian Bennion, Kris Kulp, Felice Lightstone, and Jim Felton.
- Develop SHALS (synthetic high affinity ligands) radiotherapeutics for binding with high specificity to HLA-DR10, which is a non-Hodgkin's lymphoma cell receptor, in collaboration with Rod Balhorn and Drs. Gerry and Sally DeNardo at the UC Davis Cancer Center.
- Develop reagents that will be able to detect SUMOlyation in vivo, in collaboration with Rod Balhorn and Hsing-Jien Kung at the UC Davis Cancer Center.
We have also characterized the dynamics, at multiple time scales, of apo and holo cellular retinoic acid binding protein I (CRABPI) (Krishnan et al., 2000, Biochemistry 39, 9119-9129).
Krishnan, V.V, Sukumar, M., Gierasch, L. M. and Cosman, M. (2000) "Dynamics of cellular retinoic acid binding protein I (CRABPI) on multiple time scales with implications for ligand binding," Biochemistry, 39, 9119-9129.
Cosman, M., Lightstone, F. C., Krishnan, V. V., Zeller, L., Prieto, M. C., Roe, D. C. and Balhorn, R. (2002) "Screening Mixtures of Small Molecules for Binding to Multiple Sites on the Surface of Tetanus Toxin C Fragment by Bioaffinity NMR." Chem. Res. Toxicol. 15, 1218-1228. (Cover)
Cosman, M., Krishnan, V. V. and Balhorn R. (2004) "Application of NMR Methods to identify detection reagents for use in the development of robust nanosensors, in Protein Nanotechnology: Protocols, Instrumentation and Applications" (Tuan Vo-Dinh, Ed.) Human Press, Totowa, NJ, 141-163.