Tyrosine sulfation and O-glycosylation are two post-translational modifications playing an essential rule in modulation of biological activity, protein folding and cellular communication. Here, a novel chemical approach for the synthesis of biotinylated glycosulfopeptides is described based on a combination of acid labile protecting groups, highly acid sensitive resins and two orthogonal chemoselective ligation reactions. (C) 2001 Published by Elsevier Science Ltd.