Download Associate Professor Peter Karuso Department of Chemistry and

Associate Professor Peter Karuso
Department of Chemistry and Biomolecular Sciences
Macquarie University
Quality, not quantity: The role of natural products in drug discovery
Abstract
As reactions in Nature are biased towards function, it follows that every natural
product should have a biological receptor; only if one accepts this premise can the
enormous biochemical expense of producing natural products be rationalised. Even
though natural products may not have co-evolved with human proteins, they have
emerged in nature to interact with biomolecules from a range of other species. As
Jerrold Meinwald succinctly put it, “Natural products have evolved to interact with
something, and that something may not be so different from human proteins”.[1] This
assertion is supported by a recent survey,[2] which found that 51% of the 983 new
small molecule chemical entities introduced as drugs worldwide during 1981-2006
were either natural products, natural product derivatives or natural product mimics.
Though few marine natural products have made it to market, there are many that show
potential, particularly in cancer and infectious diseases, because of their novel
structures and often potent biological activity.[3] However, the cellular target(s) and
mode(s) of action of these compounds are rarely identified. A technique that could
simultaneously and quickly identify potential protein binding partner of a natural
product would help validate marine natural products as a source for drug leads and
facilitate drug development. This lecture will outline a platform technology we call
“reverse chemical proteomics”, that combines approaches from chemistry and
molecular biology, to link small molecules with their protein binding partner(s) and
the genes for those proteins.[4-7] This technique has the potential to unlock the
secrets behind the activities of many marine natural products and expand the reach of
natural products chemistry in defining gene, cell and organism functions in health and
disease.
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A. M. Rouhi, Chemical & Engineering News 2003, 81, 77.
D. J. Newman, Journal of Medicinal Chemistry 2008, 51, 2589.
D. J. Newman, G. M. Cragg, Chimica Oggi 2006, 24, 42.
A. M. Piggott, P. Karuso, Combi. Chemistry & High Throughput Screening 2004, 7, 607.
P. P. Sche, K. M. McKenzie, J. D. White, D. J. Austin, Chemistry & Biology 1999, 6, 707.
A. M. Piggott, P. Karuso, Marine Drugs 2005, 3, 36.
A. M. Piggott, P. Karuso, ChemBioChem 2008, 7, 607.