3t1m

Publication Abstract from PubMed

Galectin-1 and galectin-3 have roles in cancer and inflammation. Galectin-1 has recently emerged as a significant protein produced by tumour cells to promote tumour development, angiogenesis and metastasis and consequently represents an important target to inhibit. The design of inhibitors targeting the carbohydrate recognition domain that is known to recognise galactose is an important approach in the fight against cancer. Based on analysis of crystal structures, we pursued the concept that if the galactose were to be replaced with talose (the C2 epimer of galactose) as a scaffold, then O2 substituents would be directed closer to the protein surface and provide opportunity to design inhibitors that are more specific toward particular galectins. Our elucidation of X-ray crystal structures of two of our synthesised talosides in complex with galectin-1 and galectin-3 provide the first atomic information on the interactions of galectins, and indeed any protein, with talosides. These results have enabled a structure-based rationale for the specificity differences shown by galectin-1 and galectin-3 toward these talosides and demonstrate new opportunities for further exploitation as specific inhibitors of galectins.

Taloside inhibitors of Galectin-1 and Galectin-3.,Collins PM, Oberg CT, Leffler H, Nilsson UJ, Blanchard H Chem Biol Drug Des. 2011 Dec 3. doi: 10.1111/j.1747-0285.2011.01283.x. PMID:22136701^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.