Research Interest:

Research in our laboratory presents numerous excellent opportunities for undergraduates of all scientific backgrounds to gain first-hand experience in their field of interest.  Perhaps most valuable is the interdisciplinary nature of our work: while students pursue research along their avenue of interest, they are also exposed to several other facets of science that may not be readily accessed in conventional organic or physical chemistry labs.  As such, over the course of the research program students can choose to gain experience in: molecular biology (e.g., PCR), bioconjugation techniques, analytical biochemistry (e.g., FPLC, SDS-PAGE) and physical techniques.  Thus, in addition to developing expertise in a specific field, students can also sample various disciplines as they decide on which area of Chemistry they wish to pursue in post-graduate work.  This multidisciplinary research program provides opportunities for collaborations between students/faculty within the Chemistry department, and in different departments at Occidental College (e.g., Biology for in vitro assays).  Students interested in conducting research in our laboratory are encouraged to contact Professor Udit.

Research Theme:

            The foremost questions in research today and the resulting innovations are increasingly focused at the interface of scientific disciplines.  For example, designing a small molecule (chemical synthesis) that can be safely injected into an individual (physiology, medicine) and then activated with light (photophysics) to kill cancer cells (oncology, cell biology).  Fields that were once isolated have merged and given rise to areas such as “bioinorganic chemistry” and “chemical genetics”, recent terminologies used to identify these novel interfacial fields of study.  It is at this interface between disciplines where our scientific interests lie.  As students of Chemical Biology, biocatalysis, bio-based materials, and chemical sensors for biological systems are among the fields that inspire studies in our laboratory. 

Research Interest #1:  Heparin Mimics Using Polyvalent Displays on Virus Particles

Constrained global supplies and pleas for pure preparations have fueled demand for easily derived and well-defined heparin synthetics.  This is particularly urgent given heparin’s increasingly recognized role in carcinogenesis,¹ necessitating precise molecular structures for unambiguous structure-function studies.  The approach we have taken to address this issue is to use virus particles as controlled, addressable polyvalent scaffolds for the display of sulfated sugars that act can as heparin mimics.  Nonnatural amino acids with bioorthogonal reactivity² and copper-catalyzed azide-alkyne cycloaddition “click” chemistry³ will be exploited to generate virus particles with pendant sulfated ligands at precise positions, allowing us to interrogate unambiguously structure-function relationships using a range of assays.  Our initial focus is on effects pertaining to carcinogenic activity (e.g., angiogenesis).

Research Interest #2:  Electrochemical Systems for P450 Cytochromes

            The growing demand for environmentally benign technologies presents significant challenges for the petrochemicals industry.⁴  This is especially true for chemical conversions involving oxidation as the reactive transition metal catalysts often employed can be highly toxic, while their synthetic limitations and complex syntheses further underscore the need for alternative strategies.  As such, the P450 cytochromes present an attractive solution: their ability to regio- and stereospecifically oxidize an array of compounds (hydrocarbons, steroids, etc.) under ambient conditions continues to fuel research into exploiting these “green” biocatalysts for commercial applications.⁵  However, a significant obstacle for practical applications using P450s is the expensive NAD(P)H cofactor, required in stoichiometric quantities for activity.  Our laboratory has focused on developing electrochemical systems that support P450 oxidation chemistry, thereby eliminating the cofactor requirement. 

 

1.  Sasisekharan, R.; Shriver, Z.; Venkataraman, G.; Narayanasami, U., Nature Reviews: Cancer 2002, 2, 521-528.

2.  Strable, E.; Prasuhn Jr., D. E.; Udit, A. K.; Brown, S. D.; Link, A. J.; Ngo, J. T.; Lander, G.; Quispe, J.; Potter, C. S.; Carragher, B.; Tirrell, D. A.; Finn, M. G., Bioconjugate Chem. 2008, 19, 866-875.

3.  Gupta, S. S.; Kuzelka, J.; Singh, P.; Lewis, W. G.; Manchester, M.; Finn, M. G., Bioconjugate Chem. 2005, 16, 1572-1579.

4.  Horvath, I. T.; Anastas, P. T., Chem. Rev. 2007, 107, 2169-2173.

5.  Gillam, E. M. J., Arch. Biochem. Biophys. 2007, 464, 2, 176-186.