发明名称 |
METHODS OF MODULATING FUNCTIONS OF POLYPEPTIDE GalNAc TRANSFERASES AND OF SCREENING SUBSTANCES THEREFOR, PHARMACEUTICAL COMPOSITIONS COMPRISING SUCH AGENTS |
摘要 |
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. These lectin domains have different binding specificities and modulate the functions of GalNAc-transferase isoforms differently. The lectin domains of GalNAc-T- and -T7 directs the glycopeptide specificities of these enzymes, while the lectin domains of GalNAc-T2 and -T3 directs broadening of donor substrate specificities to include UDP-Gal. Selective inhibitors of these functions that do not eliminate general catalytic activities are disclosed. Such inhibitors disclosed include free sugars, aryl-sugar derivatives, and glycopeptides. Inhibitors of GalNAc-transferase lectin domains are useful for altering the O-glycosylation capacity of cells, tissues, and organisms, and such agents may also interfere with other binding functions involved in intracellular sorting and secretion events. |
申请公布号 |
WO0185215(A3) |
申请公布日期 |
2002.06.27 |
申请号 |
WO2001DK00328 |
申请日期 |
2001.05.10 |
申请人 |
CLAUSEN, HENRIK;HASSAN, HELLE;REIS, CELSO, ALBUQUERQUE;BENNETT, ERIC, PAUL |
发明人 |
CLAUSEN, HENRIK;HASSAN, HELLE;REIS, CELSO, ALBUQUERQUE;BENNETT, ERIC, PAUL |
分类号 |
A61K38/00;A61K38/14;A61K38/17;C12Q1/48 |
主分类号 |
A61K38/00 |
代理机构 |
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