Matousek Josef, Poucková Pavla, Soucek Josef, Skvor Jirí
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov 27721, Czech Republic.
J Control Release. 2002 Jul 18;82(1):29-37. doi: 10.1016/s0168-3659(02)00082-2.
RNase A (bovine pancreatic ribonuclease) and BS-RNase (bovine seminal ribonuclease) are monomeric and dimeric enzymes, respectively, with aspermatogenic and antitumor activities. While the aspermatogenic and, in some experimental situations, the antitumor effects of the RNase A are only minor, the activity of BS-RNase in these phenomena is very significant. These differences can be annulled by means of conjugation of the enzymes with PEG (polyethylene glycol) chains. Aspermatogenic activity was studied histologically following subcutaneous injections of RNase A and BS-RNase conjugates in ICR mice, and the antitumor activity in athymic nude mice with growing human melanoma with i.p. injection of these conjugated ribonucleases. The experiments proved that RNase A, when conjugated to PEG, produced identical aspermatogenic and antitumour effects as BS-RNase conjugated to this polymer. Immunogenicity of RNase A and BS-RNase did not change substantially after the conjugation with PEG polymers. Binding of produced antibodies to both ribonucleases attached to PEG, however, was substantially reduced.
核糖核酸酶A（牛胰核糖核酸酶）和BS -核糖核酸酶（牛精浆核糖核酸酶）分别是单体酶和二聚体酶，具有抗精子生成和抗肿瘤活性。虽然核糖核酸酶A的抗精子生成活性以及在某些实验情况下的抗肿瘤作用较小，但BS -核糖核酸酶在这些现象中的活性非常显著。通过将酶与聚乙二醇（PEG）链偶联，可以消除这些差异。在ICR小鼠皮下注射核糖核酸酶A和BS -核糖核酸酶偶联物后，通过组织学方法研究抗精子生成活性；在患有生长中的人黑色素瘤的无胸腺裸鼠腹腔注射这些偶联的核糖核酸酶后，研究其抗肿瘤活性。实验证明，与PEG偶联的核糖核酸酶A产生的抗精子生成和抗肿瘤作用与与该聚合物偶联的BS -核糖核酸酶相同。与PEG聚合物偶联后，核糖核酸酶A和BS -核糖核酸酶的免疫原性没有实质性变化。然而，产生的抗体与附着在PEG上的两种核糖核酸酶的结合显著减少。
