Biophysical Analysis of Folic Acid-Folate Binding Protein Interaction

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DESCRIPTION (provided by applicant): The purpose of the proposed study is to examine the biophysical properties of the interaction between a folic acid (FA) conjugate and folate receptors, which are recognition components of a model drug delivery system. Understanding the various components of the drug delivery system is crucial for the development of targeted therapeutics for cancer. As a step towards that goal, a biophysical characterization of the interaction between folic acid and folate binding protein (FBP) will be undertaken using bulk measurement methods such as surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) and single molecule methods such as force pulling spectroscopy. Physical properties obtained from this study will be used as baseline measurements for the FA-FBP interaction. The results from this study will aid in the interpretation of data from multivalent interactions between FA and FBP. The specific aims of the project are to: 1) measure baseline physical properties for the FA-FBP interaction by SPR and ITC, 2) measure kinetic and thermodynamic parameters for the FA-FBP interaction by single molecule approaches, 3) investigate multivalent interactions between FA and FBP. The results of this study are expected to form the basis for further studies that will clarify the optimal number of folic acid units required for binding to a model folate receptor and provide kinetic and thermodynamic information that will lead to better designs of targeted drug-delivery systems. PUBLIC HEALTH RELEVANCE: A limitation of many medical treatments, particularly chemotherapeutics is that they are administered systemically resulting in the destruction of both sick and healthy cells. A device capable of targeting the site of action in a sick cell would be clearly preferred and most likely minimize side-effects.