Book of Abstracts - Ruhr-Universität Bochum

More documents

Recommendations

Info

P-05 ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum Solid-State Synthesis of Peptide-Tethered Pt(IV) Complexes and Their Cytotoxic Properties Sergey Abramkin, a Markus Galanski, a and Bernhard Keppler *a a University of Vienna, Faculty of Chemistry, Department of Inorganic Chemistry, Währingerstrase 42, 1090, Vienna, Austria. E-mail: sergey.abramkin@univie.ac.at Platinum-based drugs play an essential role in cancer treatment since the discovery of the anticancer drug cisplatin. Subsequent development of complexes resulted in three generations of drugs, the last one to be approved by the FDA was oxaliplatin. Side effects remain one of the main shortcomings of chemotherapy, arising from lack of specificity and inefficient cell entry. Short peptides can be used for targeting and transportation of drug molecules. They can change not only the basic parameters like lipophilicity or water solubility, but even more complex interactions of drugs with the microenvironment can be influenced. The axial ligands of Pt (IV) are the optimal site for derivatization: upon reduction they are cleaved from the prodrug, and the Pt(II) complex is released. Inefficient cell entry is the reason for higher dosage of drugs, however stimulated uptake will increase the amount of the drug, reaching the intracellular target. Cell-penetrating peptides can be used for intracellular delivery of Pt complexes; the TAT peptide is the best studied example of this group. Selectivity can be achieved using the peptides as delivery vectors. High expression of the GRP receptor in many tumors (prostate, lung, breast) makes it an interesting target for platinum conjugates. The short peptide bombesin was chosen for conjugation to Pt to investigate its influence on cytotoxic properties. H 2 N N H 2 O Pt O O O O O O O O O OH OH R R = TAT47-57(YGRKKRRQRRR) or Bombesin(QWAVGHLM) Solid-phase synthesis is a commonly used method for the preparation of peptides and their conjugates. Oxaliplatin was oxidized and two uncoordinated carboxyl groups were introduced, thereafter the complex was reacted with polymer-bound TAT and bombesin. Cleavage with TFA and purification afforded mono- and bisconjugates, characterized with ESI-MS, NMR and analytical HPLC. Synthesis and cytotoxic properties will be presented. The support of COST, the FWF, the FFG and the Austrian Council for Research and Technology Development is gratefully acknowledged. 63 H 2 N N H 2 O Pt O O O O O O O O O OH + R H 2 N N H 2 O Pt O O O O O O O O O R R
P-06 ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum Response Profile of Cancer Cells to Cisplatin Treatment Hamed Alborzinia, a Pavlo Holenya a and Stefan Wölfl *a a Ruprecht-Karls-Universität Heidelberg, Institute of Pharmacy and Molecular Biotechnology, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany E-mail: hamed.alborzinia@uni-heidelberg.de, wolfl@uni-hd.de The cell based sensor chip system BIONAS® 2500 offers the ability to measure three important parameters of cellular metabolism on line in living cell cultures: (i) glycolytic flux measured as pH change; (ii) cellular respiration (mitochondrial activity) measured as oxygen consumption; and (iii) cellular morphology, adhesion and membrane function measured as cellular impedance. These parameters are analyzed with metabolic sensor chips (SC1000) that feature the following analytical tools: (i) ion-sensitive field effect transistors (ISFETs) to record pH changes; (ii) oxygen electrodes to monitor oxygen consumption; and (iii) interdigitated electrode structures (IDES) to measure impedance under the cell layer. Cells are grown on the chip surface and all parameters are measured continuously with the electrodes on the chip surface. To work under stable conditions the medium is exchanged in short cycles with an automated fluidic system. We use this system to measure changes in cellular metabolism and morphology in response to treatment with cisplatin in different cell lines on line. Cisplatin treatment shows a well defined onset of change in acidification and impedance at about 7h and 10h respectively after treatment is started. At these time points we collected cells for further analysis of specific signalling pathways and gene expression. Protein phosphorylation of growth related signalling pathways was analyzed with a phosphoprotein ELISA micro array. Gene expression was analyzed using whole genome Affymetrix Gene Expression micro arrays. This work was in part supported by the BMBF (FKZ 01 EA 0509: “Nutrition.Net”) and the DFG Forschergruppe FOR630. 64
Page 1 and 2:
ISBOMC ‘10 5th International Symp
Page 3 and 4:
Foreword ISBOMC `10 5.7 - 9.7. 2010
Page 5 and 6:
ISBOMC `10 5.7 - 9.7. 2010 Ruhr-Uni
Page 7 and 8:
General information ISBOMC `10 5.7
Page 9 and 10:
Monday, July 5 th 2010 16:00 to 18:
Page 11 and 12:
ISBOMC `10 5.7 - 9.7. 2010 Ruhr-Uni
Page 13 and 14: ISBOMC `10 5.7 - 9.7. 2010 Ruhr-Uni
Page 19 and 20: OP-2 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 23 and 24: OP-6 ISBOMC `10 5.7 - 9.7 Ruhr-Univ
Page 27 and 28: OP-10 ISBOMC `10 5.7 - 9.7. 2010 Ru
Page 33 and 34: OP-16 Ru N Cl Cl N Ru Cl Cl ISBOMC
Page 61 and 62: P-02 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 63: P-04 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 115 and 116:
P-56 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 117 and 118:
P-58 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 119 and 120:
P-60 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 121 and 122:
P-62 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 123 and 124:
P-64 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 125 and 126:
P-66 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 127 and 128:
P-68 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 129 and 130:
P-70 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 131 and 132:
P-72 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 133 and 134:
P-74 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 135 and 136:
P-76 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 137 and 138:
P-78 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 139 and 140:
P-80 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 141 and 142:
P-82 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 143 and 144:
P-84 ISBOMC `10 5.7 - 9.7. 2010 Ruh
Page 145 and 146:
Sergey Abramkin Universität Wien,
Page 147 and 148:
Tensim Dallagi ENSCP, France t.dall
Page 149 and 150:
Prof. Dr. Toshikazu Hirao Osaka Uni
Page 151 and 152:
ISBOMC `10 5.7 - 9.7. 2010 Ruhr-Uni
Page 153 and 154:
Obiora Augustine Orakwue Hyqid Nige
Page 155 and 156:
ISBOMC `10 5.7 - 9.7. 2010 Ruhr-Uni
Page 157:
ISBOMC `10 5.7 - 9.7. 2010 Ruhr-Uni
show all

Book of Abstracts - Ruhr-Universität Bochum

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?