New muteins of RNase A with enhanced antitumor action.

Abstract:

:Monomeric bovine pancreatic RNase A has been transformed into a dimeric ribonuclease with antitumor activity (Di Donato, A., Cafaro, V. and D'Alessio, G. (1994) J. Biol. Chem. 269, 17394-17396). This was accomplished by replacing the residues located in the RNase chain at positions 19, 28, 31, and 32, with proline, leucine, and two cysteine residues, respectively, i.e. those present at identical positions in the subunit of bovine seminal RNase, a dimeric RNase of the pancreatic-type superfamily, endowed with a powerful antitumor action. However, as an antitumor agent this mutant dimeric RNase A is not as powerful as seminal RNase. We report here site-directed mutagenesis experiments which have 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 RNase.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Cafaro V,Bracale A,Di Maro A,Sorrentino S,D'Alessio G,Di Donato A

doi

10.1016/s0014-5793(98)01221-6

subject

Has Abstract

pub_date

1998-10-16 00:00:00

pages

149-52

issue

1-2

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(98)01221-6

journal_volume

437

pub_type

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