Accession Number : ADA587953


Title :   Photoinduced Partial Unfolding of Tubulin Bound to Meso-tetrakis(sulfonatophenyl) Porphyrin Leads to Inhibition of Microtubule Formation In Vitro


Descriptive Note : Journal article


Corporate Author : AIR FORCE RESEARCH LAB BROOKS CITY BASE TX HUMAN EFFECTIVENESS DIRECTORATE DIRECTED ENERGY BIOEFFECTS DIVISION/ OPTICAL RADIATION BRANCH


Personal Author(s) : McMicken, Brady ; Thomas, Robert J ; Brancaleon, Lorenzo


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a587953.pdf


Report Date : 30 Jul 2013


Pagination or Media Count : 16


Abstract : We investigated the effects of irradiating the complex formed by meso-tetrakis (sulfonatophenyl) porphyrin (TSPP) and tubulin in an attempt to induce unfolding of tubulin through the mediated photophysics of the porphyrin. Tubulin is an important protein which forms microtubules and has been a target of anticancer treatments. We used a combination of spectroscopic techniques to gain insight into the structural changes induced by the photosensitizer on the protein. In air-saturated samples, absorption and fluorescence spectroscopy show substantial bleaching of the porphyrin upon laser irradiation. The bleaching is accompanied by a sharp decrease ( 2 ns) in the average decay lifetime of the protein and a spectra shift of the dichroic spectrum consistent with a decrease of helical structure and an increase in the relative contribution of B-structure and random coil. The effect of deoxygenation of the sample (using the freeze-thaw method or the N2 purging) was also considered and the results were interpreted in the context of similar proteins. The results indicate that there is indeed significant unfolding of tubulin as a result of irradiating the bound porphyrin. Atomic force microscopy (AFM) shows that the photoinduced conformational changes inhibit the formation of microtubules in vitro.


Descriptors :   *PORPHYRINS , *PROTEINS , ABSORPTION , DEOXYGENATION , FLUORESCENCE , IN VITRO ANALYSIS , IRRADIATION , RAMAN SPECTROSCOPY , RESONANCE , SPECTROSCOPY , STEADY STATE , TUBULAR STRUCTURES


Subject Categories : Biochemistry
      Organic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE