Poly[N-(2-hydroxypropyl)meth-acrylamide] Conjugates of Bovine Seminal Ribonuclease. Synthesis, Physicochemical, and Preliminary Biological Evaluation

The synthesis of three conjugates of poly(HPMA) with bovine seminal ribonuclease (BS-RNase) differing in their structure is described. Two conjugates contained BS-RNase conjugated with the polymer via functional group situated at the end of the polymer chain (star-shaped conjugate I) or attached to the poly(HPMA) carrier via biodegradable oligopeptide spacers randomly distributed along the polymer chain (classic conjugate II). These two conjugates differ in structure, molecular weight, and molecular weight distribution. In addition, a conjugate combining the activity of two compounds, BS-RNase and doxorubicin, both attached to the same polymer chain via biodegradable spacers was synthesized (classic conjugate III). Biological activity of all BS-RNase conjugates was compared with that of free BS-RNase and to the polymer-bound anticancer drug doxorubicin (conjugate IV). Unlike the bovine pancreatic ribonuclease (RNase A), BS-RNase displays a potent antitumor activity when tested in vitro and, if adminis...