Promising College of Pharmacy Cancer Finding is June’s Monthly Publication Highlight

Jun 24, 2013

An article that identifies a previously unidentified biosynthetic pathway that holds promising opportunities for the creation of new anticancer drugs has been named the UK College of Pharmacy Publication Highlight for June.

The article is entitled “Cooperation of Two Bifunctional Enzymes in the Biosynthesis and Attachment of Deoxysugars of the Antitumor Antibiotic Mithramycin” and was published in the Angewandte Chemie International Edition.

Authors include Guojun Wang and Pallab Pahari, Postdoctoral Scholars, Madan K. Kharel, Research Assistant Professor, Steven Van Lanen, Associate Professor, and Jurgen Rohr, Professor, all from the UK College of Pharmacy’s Department of Pharmaceutical Sciences as well as Jing Chen and Haining Zhu from the UK Department of Biochemistry.

In this paper, University of Kentucky scientists discovered a unique glycosyltransferase in the natural product field able to iteratively transfer two structurally different sugars. Interestingly the glycosyltransferase acts in close cooperation with a second bifunctional enzyme, a ketoreductase/methyltransferase. The dual function of both of these co-dependent enzymes was a surprise, two essential but previously unidentified activities were discovered but not readily predicted by bioinformatic analysis. The discoveries close a gap of the mithramycin biosynthetic pathway. Results also create an opportunity for generating new mithramycin leads with altered glycosylation patterns.

“Mithramycin is a very important anticancer agent,” said Linda Dwoskin, Associate Dean for Research for the UK College of Pharmacy. “This discovery solves a riddle that has been identified by drug discovery experts around the world and equips them with the knowledge they need to identify novel anticancer solutions from natural products.”

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