THE GOVERNMENT OF THE UNITED STATES OF AMERICA; REPRESENTED BY THE SECRETARY; DEPARTMENT OF HEALTH AND HUMAN SERVICES
发明人:
SZKUDLINSKI, MARIUSZ W.,GROSSMAN, MATHIS,WEINTRAUB, BRUCE D.
申请号：
CA2253441
公开号：
CA2253441C
申请日:
1996.05.08
申请国别(地区):
CA
年份:
2013
代理人:
摘要：
The invention is directed toward a human glycoprotein hormone having at leastone, two, three, four or five basic amino acids in the .alpha.-subunit atpositions selected from the group consisting of positions 11, 13, 14, 16, 17and 20. The invention is also directed to a human glycoprotein where at leastone of the amino acids at positions 58, 63 and 69 of the .beta.-subunit of thehuman thyroid stimulating hormone are basic amino acids. The invention isfurther directed to a modified human glycoprotein hormone having increasedactivity over a wild-type human glycoprotein hormone, where the modified humanglycoprotein hormone comprises a basic amino acid substituted at a positioncorresponding to the same amino acid position in a non-human glycoproteinhormone having an increased activity over the wild-type human glycoproteinhormone. The invention is also directed to a method of constructingsuperactive nonchimeric analogs of human hormones comprising comparing theamino acid sequence of a more active homolog from another species to the humanhormone, substituting selected amino acids in the human hormone with thecorresponding amino acids from the other species, determining the activity ofthe substituted human hormones, and selecting superactive analogs from thesubstituted human hormones. The invention is also directed to nucleic acidsencoding the modified human glycoprotein hormones, vectors containing thosenucleic acids, and host cells containing those vectors.
