ISBN: 978-83-60043-10-3 - eurobic9

Recommendations

Info

Eurobic9, 2-6 September, 2008, Wrocław, Poland P87. Solid-State NMR Study of Anticancer Cisplatin Interaction with Phospholipid Bilayers M. Jensen, W. Nerdal Chemistry Department, University of Bergen, Allegaten 41, N-5007, Bergen, Norway e-mail: magnus.jensen@kj.uib.no Cisplatin has been used for many years in cancer chemotherapy of testicular cancer with a cure rate better than 90%[1]. Chemotherapy with use of cisplatin in treatment of other tumor types such as cervical cancers has also been done for many years [2-4]. It is well established that cisplatin forms platinum-DNA adducts that initiate tumor cell death [5-8]. Despite the widespread use of cisplatin in chemotherapy and its high cure rate of testicular tumors, drawbacks are side effects such as neurotoxicity and cellular cisplatin resistance. It is likely that the molecular mechanisms that take cisplatin across the cellular membrane are vital in the development of cisplatin resistance with reduced intracellular accumulation. Unfortunately, these biochemical mechanisms are not fully understood. It is therefore important to find the molecular mechanisms of how cisplatin gets across the cellular membrane and enters the cytosol, as well as establishing to what extent cisplatin interacts with the phospholipid bialyer. A consequence of cisplatin binding to phospholipids of the cellular membrane is that this can change the fluidity of the membrane and alter its function. Results of cisplatin interaction with phospholipid bilayers studied by different NMR techniques using 1H, 13C, 31P and 15N , both magic angle spinning (MAS) and static spectra, will be presented. References: [1] Bosl, G. J., Bajorin, D. F. and Sheinfeld, J. Cancer of the Testis (eds, DeVita, V. T. J., Hellman, S. and Rosenberg, S. A.) (Lippincott, Williams and Wilkins, Philadelphia, 2001). [2] Morris, M., Eifel, P. J., Lu, J., Grigsby, P. W., Levenback, C., Stevens, R. E., Rotman, M., Gershenson, D. M. and Mutch, D. G., N. Engl. J. Med. 340, 1137, (1999) [3] Rose, P. G., Bundy, B. N., Watkins, E. B., Thigpen, J. T., Deppe, G., Maimann, M. A., Clarke-Pearson, D. L. and Insalaco, S., N. Engl. J. Med. 340, 1144, (1999) [4] Keys, H. M., Bundy, B. N., Stehman, F. B., Muderspach, L. I., Chafe, W. E., Suggs, C. L., Walker, J. L. and Gersell, D., N. Engl. J. Med. 340, 1154, (1999) [5] Jamieson, E. R. and Lippard, S. J., Chem. Rev. 99, 2467, (1999) [6] Kartalou, M. and Essigman, J. M., Mut. Res. 478, 23, (2001) [7] Brabec, V. and Kasparkova, J., Drug Resist. Updates 5, 147, (2002) [8] Wang, D. and Lippard, S. J., Nat. Rev. 4, 307, (2005) _____________________________________________________________________ 206
Eurobic9, 2-6 September, 2008, Wrocław, Poland P88. The Influence of pH on the Loop-structure of an Oligonucleotide Containing Artificial Nucleobases S. Johannsen a , D. Böhme b , N. Düpre b , J. Müller b , R.K.O. Sigel a a Institute of Inorganic Chemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland e-mail: silkej@aci.uzh.ch b Faculty of Chemistry, Dortmund University of Technology, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany We synthesised a 17 nt long oligonucleotide including three imidazole moieties as nucleobase surrogates (see Figure).[1] In the absence of coordinating metal ions the oligonucleotide adopts a hairpin structure and constitutes a model system for reaction centres in ribozymes exhibiting acid-base catalysis. For a detailed analysis of the acid-base properties of each imidazole moiety we used pD-dependent 1H-NMR spectroscopy of the aromatic protons to determine the intrinsic pKa values. Starting in acidic solution, with increasing pD all imidazole protons shift to higher field, broaden out or even disappear around pD=7 and become sharper again at higher pD values. Compared to the pKa of imidazole nucleoside 5'-monophosphate (ImMP), Im8 and Im<strong>10</strong> show an increase in basicity, of up to 0.4 log units. We further calculated the NMR solution structures of the hairpin at three different pD values: pD=4.7, 7.2 and <strong>10</strong>.2. Two different, but welldefined loop structures are observed at low and high pD. In contrast, at neutral pD the loop is rather unstructured. This may result from a structural intermediate between the two loop structures, i.e., the fully protonated and completely unprotonated form. Acknowledgement: Financial support by the European ERAnet-Chemistry, the Swiss National Science Foundation (20EC21-112708 and SNF-Förderungsprofessur PP002-114759 to R.K.O.S.) and the DFG (JM1750/2-1 and Emmy Noether programme JM1750/1-3, J.M.) is gratefully acknowledged. References: [1] J. Müller D. Böhme, P. Lax, M. Morell Cerdà, M. Roitzsch, Chem. Eur. J. 2005, 11, 6246-6253. _____________________________________________________________________ 207
Page 1 and 2:
Faculty of Chemistry University of
Page 3 and 4:
International Steering Committee: M
Page 5 and 6:
Tuesday Wednesday Thursday Friday S
Page 7 and 8:
Eurobic9, 2-6 September, 2008, Wroc
Page 9 and 10:
C. Luchinat Eurobic9, 2-6 September
Page 11 and 12:
Page 13 and 14:
Page 15 and 16:
Page 17 and 18:
Page 19 and 20:
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
Page 35 and 36:
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
B. Meunier Eurobic9, 2-6 September,
Page 45 and 46:
Page 47 and 48:
Page 49 and 50:
J.J.G. Moura Eurobic9, 2-6 Septembe
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
I. Turel Eurobic9, 2-6 September, 2
Page 61 and 62:
P. Turano Eurobic9, 2-6 September,
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
A. Mokhir Eurobic9, 2-6 September,
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
J. Mattsson, B. Therrien Eurobic9,
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
E. Feese, R.A. Ghiladi Eurobic9, 2-
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
POSTERS Eurobic9, 2-6 September, 20
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156: Eurobic9, 2-6 September, 2008, Wroc
Page 187 and 188: P68. [3Fe-4S] Cluster Reduced State
Page 205: Eurobic9, 2-6 September, 2008, Wroc
Page 231 and 232: L. Lista Eurobic9, 2-6 September, 2
Page 257 and 258:
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
Page 267 and 268:
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
H. Podsiadły Eurobic9, 2-6 Septemb
Page 275 and 276:
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Page 287 and 288:
Page 289 and 290:
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Author Index Eurobic9, 2-6 Septembe
Page 333 and 334:
Bursakov ..........................
Page 335 and 336:
Hemmingsen ........................
Page 337 and 338:
Mokhir ............................
Page 339 and 340:
Smirnova...........................
show all

ISBN: 978-83-60043-10-3 - eurobic9

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

Delete template?

Save as template?