公开(公告)号：US5789195A

公开(公告)日：1998-08-04

申请号：US465500

申请日：1995-06-05

申请人： Spyridon Artavanis-Tsakonas ,  Marc Alan Telander Muskavitch ,  Richard Grant Fehon ,  Ilaria Rebay ,  Christine Marie Blaumueller ,  Scott Brockwell Shepard

发明人： Spyridon Artavanis-Tsakonas ,  Marc Alan Telander Muskavitch ,  Richard Grant Fehon ,  Ilaria Rebay ,  Christine Marie Blaumueller ,  Scott Brockwell Shepard

IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K16/18 ,  C12N15/12 ,  C12N15/05

CPC分类号： C07K16/18 ,  C07K14/705 ,  A61K38/00 ,  C07K2319/00 ,  Y10S530/839

摘要： The present invention relates to nucleotide sequences of the human Notch and Delta genes, and amino acid sequences of their encoded proteins, as well as fragments thereof containing an antigenic determinant or which are functionally active. The invention is also directed to fragments (termed herein "adhesive fragments"), and the sequences thereof, of the proteins ("toporythmic proteins") encoded by toporythmic genes which mediate homotypic or heterotypic binding to toporythmic proteins. Toporythmic genes, as used herein, refers to the genes Notch, Delta, and Serrate, as well as other members of the Delta/Serrate family which may be identified, e.g., by the methods described herein. Analogs and derivatives of the adhesive fragments which retain-binding activity are also provided. Antibodies to human Notch and to adhesive fragments are additionally provided. In specific embodiments, the adhesive fragment of Notch is that fragment comprising the Notch sequence most homologous to Drosophila Notch EGF-like repeats 11 and 12; the adhesive fragment of Delta mediating heterotypic binding is that fragment comprising the sequence most homologous to Drosophila Delta amino acids 1-230; the adhesive fragment of Delta mediating homotypic binding is that fragment comprising the sequence most homologous to Drosophila Delta amino acids 32-230; and the adhesive fragment of Serrate is that fragment comprising the sequence most homologous to Drosophila Serrate amino acids 85-283.

摘要翻译： 本发明涉及人Notch和Delta基因的核苷酸序列及其编码蛋白质的氨基酸序列，以及其含有抗原决定簇或其功能活性的片段。 本发明还涉及由介导与拓扑蛋白质的同型或异型结合的拓扑学基因编码的蛋白质（“拓扑蛋白”）的片段（称为“粘合片段”）及其序列。 如本文所用的拓扑学基因是指Notch，Delta和Serrate基因以及Delta / Serrate家族的其他成员，例如通过本文所述的方法鉴定。 还提供了保留结合活性的粘合剂片段的类似物和衍生物。 另外提供人类Notch和粘合剂片段的抗体。 在具体实施方案中，Notch的粘合片段是包含与果蝇Notch EGF样重复序列11和12最相似的Notch序列的片段; Delta介导异型结合的粘合片段是包含与果蝇Delta氨基酸1-230最相似的序列的片段; Delta介导同型结合的粘合片段是包含与果蝇三角洲氨基酸32-230最相似的序列的片段; 并且Serrate的粘合片段是包含与果糖果丝氨酸85-283最相似序列的片段。