Discovery of Carbohydrate Sulfotransferase Inhibitors from a Kinase-Directed Library

Abstract

Chemical tools for biological investigations of carbohydrate sulfotransferases—a class of enzymes that has been characterized only recently—have been developed by using a small‐molecule library‐screening approach. The inhibitor screen included 139 compounds comprising selected structures from purine libraries as well as commercially available protein‐kinase inhibitors and representatives from other kinase‐inhibitor families. Like kinases, carbohydrate sulfotransferases have attracted significant interest because of their roles in a variety of disease states including chronic inflammation and tumor metastasis.

New thiopyrazolo[3,4-d]pyrimidine derivatives as anti-mycobacterial agents

“…Unsurprisingly, structural analogues of purines have proved attractive templates for drug discovery programmes, leading to a number of significant synthetic drugs (e.g., 6-thiopurine for leukaemia, 7 acyclovir as an anti-viral 8 and allopurinol for treatment of gout 9 ). Recently, the purine core has been exploited in the synthesis of protein kinase inhibitors, 10-13 inhibitors of carbohydrate 14 and estrogen 15 sulfotransferases, as well as in compounds displaying osteogenesis-inducing activity in stem cells. 16 Compounds of this generic nature (1)(2)(3)(4)(5) have also been reported to display anti-mycobacterial activity (Fig.…”

Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1

“…lactoferrin, protamine, single chain antibodies, and surfen) (17,53); (ii) agents that block heparan sulfate metabolism (e.g. xylosides, rhodamine B, and genistein) (13,14,16); and (iii) agents that block specific enzymes in the pathway (54,55). The peptides described in this report fall into two of these inhibitor subclasses.…”

Trisubstituted Purines Are Useful Tools for Developing Potent Plant Mitogen-Activated Protein Kinase Inhibitors

“…8,18) Purine-based compounds have found new applications as inhibitors of p38 MAPK, 7) CDKs, 15) HSP90, 22) Src kinase, 23) and sulfotransferases. 24) C2, C6, and N9-trisubstituted purines have shown different inhibitory effects on p34 cdc2 /cyclin B kinase activity. 10,15) Different inhibitory potencies of Bohemine, Olomoucine, and Roscovitine versus plant MAPKs have been reported.…”