In October 2002, the Department of Chemistry received a five-year grant from the National Institute of General Medical Sciences (NIGMS, a subdivision of NIH) to build one of the nation's first Centers of Excellence in Chemical Methods and Library Development. Innovative new methodologies in Diversity-Oriented Organic Synthesis and access to high-quality libraries of diverse chemical structures provide University of Pittsburgh scientists with powerful tools to discover small molecules with a wide range of physiological properties.

The main goal of the UPCMLD is to generate novel methodologies based on original research carried out in the areas of synthesis and analysis of novel peptide mimetics (Project 1, Professor Weber & Wipf), the combination of solid phase and fluorous phase organic synthesis (Project 2, Professors Brummond & Curran), and the development and implementation of fluoropolymer-based microreactors (Project 3, Professors Nelson & Weber). Our Program applies diverging strategies to assemble architecturally unique scaffolds using transition metal catalysis, develop new separation technologies using fluorous phase synthesis strategies, design and develop microreactors for nano-scale highly parallel organic synthesis, and discover new chiral stationary phases for liquid phase chromatography. The Diversity-Oriented Synthesis Core (DOS-Core, Professors Wipf and Werner) validates library procedures and prepares and distributes the UPCMLD Library. Compounds in this library are novel and based on the methodologies that emerged from Projects 1-3.

Three recent key technological advances drive our efforts to build small molecule libraries. First, the successful completion of the Human Genome Project, which was the effort to sequence all 3 billion base pairs in the human genetic blueprint, has provided an enormous cache of biological information and identified a wealth of potential new drug targets. Second, developments in combinatorial chemistry have given academic researchers access to technologies previously available only to researchers in pharmaceutical and biotechnology companies. Third, advances in robotic technology and informatics now allow investigators to screen large numbers of compounds in a single day, orders of magnitude greater than what was possible a decade ago. Furthermore, the National Institutes of Health remain very supportive of national centers specializing in new technologies and small molecule library synthesis and are implementing a roadmap toward molecular libraries and imaging. Specifically, the Brummond, Curran & Wipf groups are part of the Molecular Libraries Screening Centers Network (UP-MLSCN).

NIGMS has also sponsored CMLDs at Boston University, the University of Kansas, and the Broad Institute of MIT & Harvard.