Attachment of O-glycans to proteins is controlled by a large family of
homologous polypeptide GalNAc-transferases. Polypeptide
GalNAc-transferases contain a C-terminal sequence with similarity to
lectins. This invention discloses that the putative lectin domains of
GalNAc-transferase isoforms, GalNAc-T4, -T7, -T2, and -T3, are functional
and recognize carbohydrates, glycopeptides, and peptides and discloses
the lectin domains of GalNAc-T1-T16. These lectin domains have different
binding specificities and modulate the functions of GalNAc-transferase
isoforms differently. Novel methods for identification of inhibitors or
modulators of binding activities mediated by lectin domains of
polypeptide GalNAc-transferases are disclosed. Direct binding activity of
GalNAc-transferase lectins has been demonstrated for the first time and
methods to measure lectin mediated binding of isolated lectins or enzymes
with lectin domains are disclosed. The present invention specifically
discloses a novel selective inhibitor of polypeptide GalNAc-transferase
lectin domains, which provides a major advancement in that this inhibitor
and related inhibitors sharing common characteristics of activity bind
lectin domains without serving as acceptor substrate for
glycosyltransferases involved in synthesis of O-glycans. This inhibitor
is represented by the .beta.-anomeric configuration of GalNAc-benzyl,
GalNAc.beta.-benzyl. Methods for inhibiting intracellular transport, cell
surface expression, and secretion of mucins and O-glycosylated
glycoproteins without affecting O-glycosylation processing are disclosed
using the novel selective inhibitor identified.