Glycomimetics: A programmed approach toward neoglycopeptide libraries

A programmed synthesis of neoglycopeptides has been developed in which two, similar or different, glycoside moieties could be attached either (i) at t he N-terminal of short peptides or (ii) one at the N-internal and the other (s) at the N-terminal site, in a highly flexible and controlled manner. A s tepwise branching of N-terminal peptides has been achieved by glycoside ald ehyde reductive amination followed by the glycoside carboxylic acid couplin g (model 1). In another approach, after N-alkylation with glycoside aldehyd e, the N-glycosylated derivative is subjected to peptide synthesis. This is then followed by the attachment of the second glycoside moiety at the N-te rminal using either glycoside aldehyde or glycoside carboxylic acid derivat ive (model 2). Alternatively, the attachment of second and third glycoside derivatives could be achieved simultaneously, by reductive amination/carbox ylic acid couplings (model 3). The methodologies presented here are highly versatile and combine diversity in both peptides/pseudopeptides and glycosi de moieties.