Covalent angiogenin/RNase hybrids

Details Covalent angiogenin/RNase hybrids Covalent angiogenin/RNase hybrids

1992-09-29

1994-02-15

Wax, Robert A.

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

435199, 514 2, 935 10, 935 14, A61K 3754, C12N 922, C12N 1500

Patent

active

052864871

ABSTRACT:
Regional mutagenesis of a gene for angiogenin to produce DNA sequences encoding mutant proteins having increased angiogenic activity are disclosed. Expression vectors containing these sequences are introduced into host cells and direct the production of mutant angiogenic proteins with markedly increased angiogenic activity. Replacement of amino acids in a region at or corresponding to residues 8-22 of angiogenin, with other amino acids, in particular, with amino acids corresponding to residues 7-21 of RNase, unexpectedly yields a mutant angiogenin/RNase hybrid protein with 10-fold increased angiogenic potency in the chorioallantoic membrane assay. Other in vivo and in vitro angiogenin-related activities are altered in the mutant hybrid protein. Mutant angiogenin/RNase hybrid proteins according to the present invention are useful therapeutic compositions to promote the development of a hemovascular network in a mammal or to promote wound healing, in particular, healing of torn or traumatized fibrocartilage material.

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