NEW MUTEINS OF RNASE-A WITH ENHANCED ANTITUMOR ACTION

Citation
V. Cafaro et al., NEW MUTEINS OF RNASE-A WITH ENHANCED ANTITUMOR ACTION, FEBS letters, 437(1-2), 1998, pp. 149-152
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology",Biophysics
Journal title
FEBS letters → ACNP
ISSN journal
0014-5793
Volume
437
Issue
1-2
Year of publication
1998
Pages
149 - 152
Database
ISI
SICI code
0014-5793(1998)437:1-2<149:NMORWE>2.0.ZU;2-T
Abstract
Monomeric bovine pancreatic RNase A has been transformed into a dimeri c ribonuclease with antitumor activity (Di Donate, A., Cafaro, V, and D'Alessio, G, (1994) J. Biol. Chem. 269, 17394-17396), This was accomp lished by replacing the residues located in the RNase chain at positio ns 19, 28, 31, and 32, with proline, leucine, and two cysteine residue s, respectively, i,e. those present at identical positions in the subu nit of bovine seminal RNase, a dimeric RNase of the pancreatic-type su perfamily, endowed with a powerful antitumor action. However, as an an titumor agent this mutant dimeric RNase A is not as powerful as semina l RNase, We report here site-directed mutagenesis experiments which ha ve led to the identification of two other amino acid residues, glycine 38 and 111, whose substitution in the polypeptide chain of the first generation dimeric mutant of RNase A, is capable of conferring to the mutein the full cytotoxic activity characteristic of native seminal RN ase, (C) 1998 Federation of European Biochemical Societies.