Some biological actions of PEG-conjugated RNase A oligomers

P., POUCKOVA, J., SKVOR, G., GOTTE, F., VOTTARIELLO, J.T., SLAVIK, J., MATOUSEK, D.V., LAURENTS, M., LIBONATI, J., SOUCEK,

Abstract:

Previously we have shown that monomeric RNase A has no significant biological activity, whereas its oligomers (dimer to tetramer) prepared by lyophilizing from 50% acetic acid solutions, show remarkable aspermatogenic and antitumor activities. Furthermore, conjugates prepared by chemical binding of native RNase A to polyethylene glycol (PEG) have shown a significant aspermatogenic and antitumor activities. In this work we show that the chemical conjugation of PEG to the RNase A C-dimer, and to the two RNase A trimers (NC-trimer and C- trimer) decreases the aspermatogenic activity of the oligomers while increasing their inhibitory activity on the growth of the human UB900518 amelanotic melanoma transplanted in athymic nude mice. Moreover, the PEG-conjugated RNaseAoligomers are devoid, like the free oligomers, of any embryotoxic activity.