Vicente, Graca - Louisiana State University

个人简介

Bachelor's Degree(s): University of Aveiro, 1986 PhD: University of California Davis, 1990 PostDoc: Univ Bourgogne 1991, Univ Geneva 1992, ITQB 1993

研究领域

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Our research centers on development of new fluorescent porphyrin-based macrocycles for application in medicine [e.g. diagnosis, photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer], and the study of their physicochemical and biological properties. Porphyrin-type compounds bear a number of key photochemical, photophysical and biological properties that make them highly desirable for medical applications: they absorb strongly in the visible region of the optical spectrum, have low dark toxicities, are chemical stable, have affinity for serum proteins and favorable pharmacokinetic properties, and form very stable complexes with a variety of metal ions. Several porphyrin-type compounds are currently in various stages of preclinical or clinical development as phototherapeutic agents; Photofrin® and VisudyneTM are two FDA-approved porphyrin-based photosensitizers for PDT. The new macrocycles under development in our group are obtained either by derivatization of naturally occurring porphyrins (hemin and chlorophyll-a), or the preparation of new synthetic macrocycles containing special features for enhanced biological activity. Special emphasis is placed on the synthesis of polypyrroles containing both lipophilic side groups for interaction with cell membranes, and hydrophilic groups for solubilization in the blood stream, and with intense long-wavelength absorptions for enhanced photoactivity. We investigate the mechanisms of cell uptake, retention and subcellular localization of the new compounds, and the influence of hydrophobicity, aggregation, charge and metalation on their biological activity. The spectroscopic characteristics of the new compounds and their acid-base properties, aggregation behavior, protein-binding affinities and interactions with DNA are studied in our laboratories, using primarily UV/Vis spectroscopy and fluorescence microscopy. The most promising candidates are further evaluated in animal models. Fluorescence of H2DCP localized in the lysosomes of human keratinocyte HaCaT cells. X-ray structure of Zn(II)-TCP, a promising new BNCT agent. The study of heme polymerization and aggregation is also a goal of our research. These are important reactions in, for example, the treatment of hepatic porphyrias, which are genetic disorders of heme biosynthesis, and in malaria treatment. New synthetic routes to covalently-linked porphyrin arrays are also goals of our research. These systems display unique photoelectronic properties and have potential applications as mimics of light-harvesting in photosynthesis, and as electron/energy transfer moieties in molecular wires. A variety of model structures have been prepared by us and others, containing two or three porphyrin units, either directly coupled, bridged by coplanar aromatic systems, or beta-fused. Coplanar-linked porphyrin arrays are believed to lead to more efficient energy- and electron-transfer superstructures. Metalloporphyrins are also synthesized in our laboratories for application as catalysts, in relation to their biological functions in hemoproteins and cytochrome P450.