Biophysics

Boston University, 2000-02
Advisor: Jonathan P Lee, PhD, Department of Chemistry
Project: Studies of the acid dissociation behavior in a dicarboxylic acid dipeptide

For my current project, I am employing a novel pro-drug strategy to design a ribonuclease-based HIV therapy. We have designed a zymogen that will be activated only in the presence of HIV protease, and, following activation, will cleave the cells' RNA and lead to apoptosis. In this design, RNase A was circularly permutated and a linker was added between the N and C termini that blocks the active site. This linker contains a substrate for HIV protease. It is our hope that this work will result in the production of a biotherapeutic that is selectively toxic toward HIV-infected cells. 

Turcotte RF, Lavis LD, Raines RT. 2009. Onconase cytotoxicity relies on the distribution of its positive charge. FEBS J 276:3846-57. PMCID: 2754565

Turcotte RF, Raines RT. 2008. Design and Characterization of an HIV-Specific Ribonuclease Zymogen. AIDS Res Hum Retroviruses Nov 11.

 Turcotte RF, Raines RT. 2008. Interaction of onconase with the human ribonuclease inhibitor protein. Biochem Biophys Res Commun 377:512-4. PMCID: 2605674

Turcotte RF, Raines, RT. Role of Positive Charge Distribution in the Cellular Internalization and Cytotoxicity of Onconase: Implications for Cytosolic Biotherapeutics. Endocrine Grand Rounds, University of Wisconsin - Madison, Madison, WI, October 4, 2007.

Turcotte RF, Raines RT. Role of Positive Charge in the Cellular Internalization and Cytotoxicity of Onconase. 27th Midwest Enzyme Chemistry Conference, University of Illinois at Chicago, Chicago, Illinois, 2007.

Turcotte RF, Raines RT. Net Charge is Not the Primary Determinant of Onconase Cytotoxicity. American Chemical Society 233nd National Meeting & Exposition, Chicago, Illinois, 2007.