Biochemical and Biophysical Research Communications. 2008 Dec 12;377(2):512-4. Epub 2008 Oct 16. [Link]
Turcotte RF, Raines RT.
Medical Scientist Training Program and Biophysics Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
One of the tightest known proteinâ€“protein interactions in biology is that between members of the ribonuclease A superfamily and the ribonuclease inhibitor protein (RI). Some members of this superfamily are able to kill cancer cells, and the ability to evade RI is a major determinant of whether a ribonuclease will be cytotoxic. The archetypal cytotoxic ribonuclease, onconase (ONC), is in late-stage clinical trials for the treatment of malignant mesothelioma. We present here the first measurement of the inhibition of the ribonucleolytic activity of ONC by RI. This inhibition occurs with Ki = 0.15 μM in a solution of low salt concentration.
Keywords: Cancer; Cytotoxin; Enzyme inhibition; Onconase; Ribonuclease; Salt concentration
Abbreviations: RNase A, bovine pancreatic ribonuclease; RI, ribonuclease inhibitor protein; PBS, phosphate-buffered saline; RNase 1, human pancreatic ribonuclease; ONC, onconase