CHED 836

Four N-alkylaminooxy amino acids have been developed for the efficient synthesis of neoglycopeptides. Each is synthesized from readily available precursors in 22-56% yield and can be incorporated into peptides via Boc-chemistry-based solid-phase peptide synthesis. The peptides resulting from three of the four amino acids can be chemoselectively glycosylated at the aminooxy side chains with standard unprotected sugars to form neoglycopeptides. The three amino acids allow attachment of sugars at two-, three-, or four-atom distances from the peptide backbone, and the nature of the aminooxy side chain ensures that attached sugars adopt cyclic conformations. These derivatives provide convenient access to combinatorial arrays of biologically relevant neoglycopeptides that may be used to probe the effects of attached sugars on the structure and function of peptides and proteins. Here we report the synthetic procedures and recent investigations into the stability of the neoglycopeptides.