User:Hoffmacs/Ipglycermides

Ipglycermides are non-natural macrocyclic peptide (MCP) inhibitors of cofactor independent phosphoglycerate mutases (iPGM) discovered by the research laboratories of Dr. James Inglese of the National Institutes of Health and Prof. Hiroaki Suga of the University of Tokyo. These high affinity molecules were discovered using affinity selection from an RNA-encoded MCP library having a theoretical size of trillions of members, though in practice the numbers are several orders of magnitude lower, however, significantly larger than anything possible with standard small molecule chemical libraries typically applied in high throughput screening (HTS). The initially RaPID selected ipglycermides using C. elegans iPGM as the selection target were Ce-1 and Ce-2, 14 amino acid cyclic lariat peptides containing an 8-member peptide ring and six amino acid linear sequence terminating in Cy14. Ce-1 and Ce-2 differed by a single amino acid at position 7, histidine vs. tyrosine, respectively [ref Yu et al. (2017)]. Subsequent sequence activity relationship studies demonstrated that additional amino acid sequence variation was possible [ref Weidmann et al (2021)] suggesting that the initially identified Ce-1 and Ce-2 reflected a fraction of the potential library size and diversity. The limited number of ipglycermides initially identified may reflect the restricted library size, selection efficiency or a combination of both.

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