WSS2220, a novel cyclic tetrapeptide with a new sulfonoamino acid, exhibits potent and selective inhibitory activity against GlyT1

In the course of our screening program for novel glycine transporter inhibitors, we obtained a novel cyclic tetrapeptide (WSS2220) from the culture broth of Nonomuraea sp. The structure of WSS2220 was elucidated based on physicochemical data. WSS2220 contained a novel amino acid (4-oxo-3′-sulfoisoleucine), the absolute stereochemistry of which was determined by chemical modifications and the modified Mosher’s method. WSS2220 selectively inhibited glycine transporter type1 with an IC50 of 20 nM.