Expanding Diversity: Modification of Linear and Cyclic Peptides by C-Glycosylation and N-Methylation

Abstract

The stereochemical versatility of carbohydrates provides much structural diversity and has made them useful also as peptidomimetic scaffolds [1], Just as peptides can be rendered more stable by backbone modifications including N-methylation and amide bond replacements [2], carbohydrates can likewise be stabilized by replacement of their vulnerable hemiacetal linkages. C-sugars are derivatives of carbohydrates in which the anomeric carbon is replaced by a methylene unit [3,4]. Carbohydrates are known to be involved in numerous biological processes such as cell-cell recognition [5]. Some glycoconjugate vaccines are being tested for prostate cancer [6]. C-sugars appear as very attractive substrates because of their increased stability especially against hydrolysis, but at the same time their structural and chemical properties are similar to O-glycosides [3,4]. This explains the increase of interest for C-glycosides [7]. Accordingly, we have initiated the synthesis of different pseudoglycopeptides.