Some biological actions of PEG-conjugated RNase A oligomers.
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 RNaseA oligomers are devoid, like the free oligomers, of any embryotoxic activity.
Pouckova
P
P
Institute of Hematology and Blood Transfusion, 12820 Prague, Czech Republic.
Skvor
J
J
Gotte
G
G
Vottariello
F
F
Slavik
J T
JT
Matousek
J
J
Laurents
D V
DV
Libonati
M
M
Soucek
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000988:Antispermatogenic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D019281:Dimerization; D004622:Embryo, Mammalian / Q000187:drug effects; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000494:pharmacology*; D013091:Spermatogenesis / Q000187:drug effects
D000970:Antineoplastic Agents; D000988:Antispermatogenic Agents; D010446:Peptide Fragments; D011092:Polyethylene Glycols; D012259:Ribonuclease, Pancreatic