CEPCEB Members

Michael C. Pirrung Professor and UC Presidential Chair Department of Chemistry University of California Riverside, CA 92521-0403 Phone: (951) 827-2722 Fax: (951) 827-2749 Areas of Expertise Synthetic Chemistry Microarray Fabrication, Use and Analysis
Background   Description of Research Key Areas of Expertise Ethylene Biosynthesis and Action Combinatorial Synthesis Chemical Genetics Current Laboratory Personnel Selected Publications (Bibliography page)

Background

I was trained in synthetic organic chemistry in the laboratories of Clayton Heathcock and Gilbert Stork. I was on the Stanford faculty during the 1980s, where our research in plant hormones began. I was then a member of the scientific working group that started the company Affymax, which was a major success among combinatorial chemistry start-ups. My work there focused on the development of microarrays, which were commercialized by their sister company Affymetrix. I left Affymax to join the Duke faculty in 1990, where I founded and directed the Program in Biological Chemistry, an interdepartmental graduate training group. In 2004 I came to UC-Riverside.

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Description of Research

Key Areas of Expertise

A major portion of our lab works in synthetic chemistry. This ranges from target-directed synthesis of biologically active natural products, to development of synthetic and combinatorial chemistry methodology, to the preparation of combinatorial libraries, to oligonucleotide synthesis. We also develop novel methods for microarray fabrication and use aimed at increasing the fidelity of microarray analysis. This broad program utilizes a wide range of instrumentation, including several types of chromatography, optical spectroscopy, automation, and imaging.

We put forth the accepted chemical mechanism for ethylene biosynthesis and have been working toward a deeper understanding of the ethylene-forming enzyme as an available and significant member of the class of non-heme iron oxidizing enzymes. Ethylene is important because of the role it plays in the regulation of such important plant physiological processes as ripening, senescence, and germination. We likewise put forth a mechanism for the action of ethylene on its membrane-bound, copper-containing receptor, and are working toward proof of this mechanism through theoretical, structural and dynamic studies of copper complexes with ethylene and other known ethylene receptor ligands.

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Combinatorial Synthesis

This work focuses on the efficient preparation of large libraries of compounds that can be screened for a desired activity, as well as development of novel methods for combinatorial synthesis. We execute both solid-phase synthesis and parallel, solution-phase synthesis, and are exploring a wide variety of tactics to accelerate organic reactions to speed library preparation. These include unusual energy sources (UV light, microwave irradiation, sonication) and medium effects (aqueous solutions, ionic liquids). One particular interest is libraries of biologically active natural products. The relevance of this focus to broad-based discovery of active compounds is the conservation of biological signaling pathways. The commonality of macromolecular structures and functions throughout life, while certainly not as universal as the genetic code, is the basis of the well-established biological activity of secondary metabolites in disparate kingdoms. Thus, molecular libraries inspired by natural products have a high likelihood of exhibiting activity regardless of the biological target. These natural products are chosen for their relevance to pleiotropic biological processes (e.g., kinase or protease inhibition). This strategy addresses one of the major unresolved challenges of combinatorial chemistry, library design.

Chemical Genetics

With collaborating biology groups, this research provides an immediate application - the identification of agents that can mimic genetic knockouts - for the libraries we prepare. We work in organisms such as Drosophila, mosquito, and Arabidopsis. Additionally, we are developing strategies for identification of the targets of uniquely active small molecules identified in phenotypic screens using both systematic [methyl scanning] and affinity-based [tagged library] approaches.

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Current Laboratory Personnel

POSTDOCS:

Name	Research Focus
Walter Affo	Synthesis of combinatorial libraries of insulin mimics
Sankar Guchhair	Novel combinatorial reactions
Hyunsoo Kim	Molecular biology and RNA microarray analysis
Valeri Pavlov	DNA synthesis and microarray fabrication
Vipul Rana	DNA synthesis and microarray fabrication
Aparna Tanksale	Screening and mechanism of anti-birals and anti-diabetics
Chiyi Xiong	Synthesis of peptidomimetics

GRADUATE STUDENTS :

Name	Research Focus
Liu Deng	Synthesis of combinatorial libraries of insulin mimics
Irwin Loh	Total synthesis of hibiscone
Jianmei Wang	Novel combinatorial reactions
Yunfan Zou	Models for the ethylene receptor

Selected Publications (Bibliography page)

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