Krishnan P. Nambiar
Ph.D. University of New Brunswick, Canada
Our research focuses on understanding the chemical interactions involved in macromolecular recognition relevant to biological systems and the utilization of the resulting information in the design of novel molecules with chemical and biological applications.
Peptides and Peptidomimetics
We have been investigating the parameters that influence the folding of peptides into specific secondary structures. We have shown that short a-helices can be stabilized by end capping. We have been active in the area of stabilizing beta ribbon structures as well. We have shown that incorporation of a strain-free disulfide bridge between two peptide strands results in a large increase in the stability of b-ribbon structures formed by the peptides. In addition, we have designed and synthesized a turn structure which upon incorporation into a peptide forces it to adopt a stable beta ribbon structure.
This project involves the chemical synthesis of an unnatural analog of DNA having the bases connected to the sugar via a-anomeric linkages rather than the natural b- linkages, and the phosphodiester linkage replaced with a sulfone linkage, in order to study their chemical and biological properties.
Another project involves the design and synthesis of organic catalysts. By synthesizing a designed binding pocket and incorporating specific catalytic functional groups at the mouth of the cavity, we hope to attain substrate binding followed by catalysis. We designed an organic molecule (compound I, Figure 2) with a hydrophobic binding pocket, whose synthesis is now half way through.
Education, Awards and Professional Highlights
- Appointed to UC Davis faculty (1987)
- Research Fellow / Research Associate, Harvard University (1978-1987)
- Ph.D. University of New Brunswick, Canada (1978)
- M.S. University of Calicut, India (1973)
- B.S. University of Calicut, India (1971)
- Stewart, D.N., Lango, J, Nambiar, K.P., Falso, J.S., Fitzgerald, P.G., Rocke, D.M., Hammock, B.D., and Buchholz, B.A., Molecular Vision, 19, 463-475 (2013).
- "Quantitation of [5-14CH3]-2R,4'R,8'R)-!-Tocopherol in Humans" Chuang JC, Matel HD, Nambiar KP, Kim S, Fadel JG, Holstege DM, Clifford AJ., J Nutr. First published ahead of print June 29, 2011 as doi: 10.3945/jn.111.138925. http://jn.nutrition.org/
- Isolation and characterization of a snake venom metalloprotease inhibitor from California ground squirrel (Spermophilus beecheyi) blood sera Biardi, J.E., Ho, L.C., Marcinczyk, J.M., and Nambiar, K.P. Toxicon 58:486-493. (2011).
- Development and validation of a rapid and sensitive fluorescence-based assay of snake venom metalloprotease activity. Biardi, J.E., Nguyen, K.T., Lander, S., Whitley, M., and K.P. Nambiar. Toxicon 57:342-347 (2011).
- Structural Characterization of !-Helices of Implicitly Solvated Poly-Alanine., Couch, V. A.; Cheng, N.; Nambiar, K. P.; Fink, W. H. Journal of Physical Chemistry B (2006), ASAP Article; DOI: 10.1021/jp055209j
- Design, Synthesis and Incorporation in Peptides of a "-turn Mimetic, Janardhanam, S.; Balachari, D. and Nambiar, K.P., Peptides: Proceedings of the 2nd International/17th American Peptide Symposium. Richard Houghton (Eds), Kluwer Academic Publishers, 2001 , 440-441
- "Strain-Free Disulfide Bridge and Stabilization of "-Ribbon Structures in Short Peptides" Nambiar, K.P, Janardhanam, S. and Balachari, D., Peptides for the New Millenium, Proceedings of the 16th American Peptide Symposium, G.B Fields, J.P. Tam and G. Barany (Eds), Kluwer Academic Publishers 2000, 311-312.
- "End Capping and Helix Stabilization in Short Peptides", Reddy, H. K. and Nambiar, K. P., Peptides: Frontiers of Peptide Science, Proceedings of the 15th American Peptide Symposium, J.P. Tam and P.T.P. Kaumaya (Eds), Kluwer Academic Publishers, 1999, 114-115.
- "Redesigning Nucleic Acids", Benner S.A. et al, Pure and Appl. Chem., 70, 263-266 (1998).
- "The Role of a strain free disulfide bridge in stabilizing "-sheet structures in short peptides", Janardhanam, S., Balachari, D., Corson, D.T. and Nambiar, K.P., Proceedings of the 14th American Peptide Symposuim, Peptides: Chemistry, Structure andBiology. Pravin T.P. Kaumaya and Robert S. Hodges (Eds), Mayflower Scientific Ltd, 575-576 (1996).
- "Extraordinary Helicity in Short Peptides via End Capping Design", Forood, B., Reddy, H. R. and Nambiar, K. P. J. Am. Chem. Soc., 116, 6935-6936 (1994).
- "Stabilization of "-Ribbon Structures in Peptides using Disulfide Bonds", Aberle, A. M., Heeb, N. V. and Nambiar, K. P. Biochem. Biophys. Res.Commun., 200, 102-107 (1994).
- "Synthesis of Oligodeoxynucleotides Containing 2-Thiopyrimidine Residues -A New Protection Scheme", Kuimelis, R. G. and Nambiar, K. P.Nucleic Acids Research, 22, 1429-1436 (1994).
- "An Efficient Synthesis of !-Purine Nucleosides of 2-desoxyribofuranose and 2-Deoxyribopyranose"Salvasekaran, J. and Nambiar, K. P.J. Chem. Soc. Chem. Commun., 1009-1010 (1994).
- "Stabilization of !-Helical Structures in Short Peptides via End Capping", Forood, B., Feliciano, E. J. and Nambiar, K. P., Proc. Natl. Acad. Sci. USA, 90, 838-842 1993).
- "Efficient Desulfurization of 2-Thiopyrimidine Nucleosides to the Corresponding 4-Pyrimidinones", Kuimelis, R. G. and Nambiar, K. P., Tetrahedron Letters, 34, 3813-3816 (1993).
- " A stereoselective synthesis of !- and "- 2'-Deoxy-2-thiouridine", Kuimelis, R. G., Hope, H. and Nambiar, K. P., Nucleosides and Nucleotides, 12 , 737-755 (1993).
- " The Ribonuclease from an Extinct Bovid Ruminant " Stackhouse, J. Presnell, S. R., Mcgeehan, G., ambiar, K. P. and Benner, S. A.; FEBS Letters, 262, 104-106 (1990).\
- "6-Fluorocholesterol as a growth factor for the yeast mutant GL 7", Zundel, M., Nambiar, K. P., Boswell, G. and Bloch, K., Biochemistry, 28, 5161-5164 (1989).
- "Expression in E. Coli of a gene coding for Bovine Pancreatic Ribonuclease-A", Nambiar, K. P, Stackhouse, J., Presnell, S.R.and Benner, S.A., Eur. J. Biochemistry, 163, 67-71 (1987).
- Stackhouse, J., Presnell, S. R. and Benner, S.A., Enzymes as Catalysts in Organic Synthesis, M. P. Schneider Ed.,Ulm, 325-340, Series C, Vol. 178, June 1985.
- "Dynamic Transduction of Energy and Internal Equilibria in Enzymes", Stackhouse, J., Nambiar, K. P., Burbaum, J., Stauffer, D. M. and Benner, S.A., J. Am. Chem. Soc.107, 2757-2763 (1985).
- "A Stereochemical Imperative in Dehydrogenases: New Data and Criteria for Evaluating Function-Based Theories in Bioorganic Chemistry", Benner, S. A., Nambiar, K. P. and Chambers, G. K., J. Am. Chem. Soc.107, 5513-5517 (1985).
- "Total Synthesis and Cloning of a Gene Coding for Ribonuclease-S Protein", Nambiar, K. P., Stackhouse, J., Stauffer, D. M., Kennedy, W. P., Eldredge, J. K. and Benner, S. A., Science, 223, 1299-1301 (1984).
- "A Mechanistic Basis for the Stereospecificity of Enzymatic Transfer of Hydrogen from Nicotinamide Cofactors", Nambiar, K. P., Stauffer, D. M., Kolodziej, P. A. and Benner, S. A.,J. Am. Chem. Soc.105, 5886-5890 (1983).
- "Asymmetric Total Synthesis of Erythromycin 1. Synthesis of an Erythronolide-A Secoacid Derivative via Asymmetric induction", Woodward, R. B., Logush, E., Nambiar, K. P., Sakan, K., Ward, D. E., et al., J. Am. Chem. Soc.103, 3210 (1981).
- "Asymmetric Total Synthesis of Erythromycin 2. Synthesis of Erythronolide-A Lactone System", Woodward, R. B., Logush, E., Nambiar, K. P., Sakan, K., Ward, D. E., et al., J. Am. Chem. Soc.103, 3213 (1981).
- "Asymmetric Total Synthesis of Erythromycin 3. Total Synthesis of Erythromycin", Woodward, R. B., Logush, E., Nambiar, K. P., Sakan, K., Ward, D. E., et al., J. Am. Chem. Soc.103, 3215 (1981).
- "Total Synthesis of Erythronolide-A", Corey, E. J., Hopkins, P. B., Kim, S., Yoo, S., Nambiar, K. P. and Falck, J. R., J. Am. Chem. Soc.101, 7131 (1979).
- "Synthesis of Chasmanine and 13-Desoxydelphonine: A Preferred Route to the Aromatic Intermediate", Tsai, T. Y. R., Nambiar, K. P., Krikorian, D., Botta, M., Marini-Bettolo, R. and Wiesner, K., Can. J. Chem. 57, 2124 (1979).
- "A New Stereospecific Synthesis of Chasmanine and 13-Desoxydelphonine", Wiesner, K., Tsai, T.Y. R. and Nambiar, K. P., Can. J. Chem. 56, 1451 (1978).
- "The Construction of Substituted Denudatine System by Diene Addition", Wiesner, K., Tsai, T. Y. R., Dmitrienko, G. I. and Nambiar, K. P., Can. J. Chem. 54, 3307 (1976).