Microsoft word - frosch 06 oral.doc
6 Spectroscopy in chemical, pharmaceutical and environmental analyses
Vibrational Spectroscopic Investigation of Drug-Target-Interactions in
1 Institut für Physikalische Chemie, Universität Jena, Helmholtzweg 4, D-07743 Jena, Germany
2 Institut für Photonische Technologien, Albert-Einstein-Straße 9, D-07745 Jena, Germany
Raman and IR spectroscopy was applied an investigation of the molecular mode of
action of antimalarial active agents with their biological targets [1-8].
While Malaria is still one of the most devastating infectious diseases on earth [9, 10],
resistances against established drugs arise on a global scale [11-13]. However, the molecular mode of action of those key drugs, e.g. chloroquine, is not well understood. It is believed that this class of antimalarials acts in the red blood cell state of the plasmodium’s asexual life cycle in the human body. At this stage the drugs interfere with the detoxification process of the hemoglobin digestion by-products [14, 15].
In this contribution we demonstrate the high potential of Raman spectroscopy for a
non-invasive, label-free, molecular investigation of important antimalarial active agents [1-5] and the malaria pigment hemozoin  as well as their molecular interactions [7, 8]. UV resonance Raman microscopy was applied for a very sensitive and selective investigation of different drugs under physiological conditions [1-4]. The experimental results have been confirmed by means of DFT calculations. Also the biological target hemozoin was localized in the infected cells and structurally investigated . These in situ
results were compared with spectra of extracted hemozoin as well as with synthesized ß-hematin  and the Raman spectra of dimeric unit cell of the malaria pigment were calculated for the first time. A new, versatile device for Raman difference spectroscopy was designed and allows for a gentle, sensitive, selective, and precise investigation of drug target interactions .
The understanding of molecular vibrations of the active agents and the targets and
how they may change upon molecular interactions with each other will inform drug chemistry and help fighting back against Malaria.
T. Frosch, M. Schmitt, G. Bringmann, W. Kiefer, J. Popp, J. Phys. Chem. B 111 (2007) 1815-1822.
T. Frosch, M. Schmitt, J. Popp, Anal. Bioanal. Chem. 387 (2007) 1749-1757.
T. Frosch, M. Schmitt, J. Popp, J. Phys. Chem. B 111 (2007) 4171-4177.
T. Frosch, M. Schmitt, T. Noll, G. Bringmann, K. Schenzel, J. Popp, Anal. Chem. 79 (2007) 986-993.
T. Frosch, M. Schmitt, K. Schenzel, J. H. Faber, G. Bringmann, W. Kiefer, J. Popp, J. Biopolymers 82 (2006) 295-300.
T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, J. Popp, J. Phys. Chem. B 111 (2007) 11047-11056.
T. Frosch, B. Kuestner, S. Schluecker, A. Szeghalmi, M. Schmitt, W. Kiefer, J. Popp, J. Raman Spectrosc. 35 (2004) 819-821.
T. Frosch, T. Meyer, M. Schmitt, J. Popp, Anal. Chem. 79 (2007) 6159-6166.
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A D M I E MEASUREMENTS AND INSTRUMENTS SECTION PROGRAMMABLE DISPLAY & DATA RECORDERS SCOPE This technical description covers the technical characteristics and the required tests for Programmable Display and Data Recorders to be installed in Transmission Substations. USE These Programmable Display and Data Recorders will accept at its inputs analogue DC signals for m
MP ROAD DEVELOPMENT CORPORATON LTD. BHOPAL LIT OF QUALIFIED BIDDER FOR ISSUANCE OF REQUEST FOR PROPOSAL DOCUMENT BIAORA(NH-12) ROAD NAME OF BIDDER M/s VIJAY INFRASTRUCTURE-M/S AZTEK INFRASTRUCTURE PVT. LTD. (CONSORTIUM) LUCKNOW M/s ECI ENGINEER & CONSTRUCTIONS LTD.-M/S SMS INFRASTRUCTURE LTD. (CONSORTIUM), HYDERABAD M/s GANNON DUNKERLEY & CO LTD. NEW DELHI M/s V