The invention is directed toward a human glycoprotein hormone having at
least one, two, three, four, or five basic amino acids in the
.alpha.-subunit at positions selected from the group consisting of
positions 11, 13, 14, 16, 17, and 20. The invention is also directed to a
human glycoprotein where at least one of the amino acids at position 58,
63, and 69 of the .beta.-subunit of the human thyroid stimulating hormone
are basic amino acids. The invention is further directed to a modified
human glycoprotein hormone having increased activity over a wild-type
human glycoprotein hormone, where the modified human glycoprotein
comprises a basic amino acid substituted at a position corresponding to
the same amino acid position in a non-human glycoprotein hormone having
an increased activity over the wild-type human glycoprotein hormone. The
invention is also directed to a method of constructing superactive
nonchimeric analogs of human hormones comprising comparing the amino acid
sequence of a more active homolog from another species to the human
hormone, and selecting superactive analogs from the substituted human
hormones. The invention is also directed to nucleic acids encoding the
modified human glycoprotein hormones, vectors containing those nucleic
acids, and host cells containing those vectors.