Thioether ligand containing copper complexes; Modeling PHM and DβH proteins

ioether Ligand Containin Modeling PHM an Y~/unhoLee. department of Chemistry, The Johns Hopkins University, United States Don&&on Lee, Department of Chemistry, Chonbuk National Um’versity, Korea Karlin, Department of Chemistry, The Johns Hopkins University, Uvlited States ah, Department of Chemistry, Chonbuk National Universily, Korea The ~nvoivement of a sulfur atom as a ligand in copper complexes is ~~~~e~tlyof cOnsiderable iMXW% in bioinor chemistry. Of special interest are the active sites of PHM (pepti~ylgly~i~e ~-hydorxyl~ti~g rn~~~~~~~~~as~~and ~~~pamine ~~hyd~o~yiase)containing a methionine residue as one of the ligands of a central ~ata%~ti~copper. AS syn models, we have prepared Cu’ and CU’~complexes with a seriesof novel mono- or ~i~~~~eat~~g ligands ~~~~~~~i~g ath~oe~~e~ (LNNs-l= Methyl-(2-phenet~ylslllfanyl-propyl)-(2-pyriil”.in-2-yI-ethyP)-amine, sulfur atom (Figure I). Ligands LNNs-’and LNNsep LNNs-*= (2-Benzylsulfanyl-propyl)-methyl-(2-pyridin-2-yl-ethyl)k&/R amine) were designed to possessa potential internal ligand-derived , -I”G benzylic substrate.In order to more closely mimic the active sites of e (-5 the enzymes we also prepared methionine amino-acid based monoi-G&S-I: R - phemthyl v-5 IYNs.2: R=betayl ligands. The copper complexes ;LMET-PY1 ) and dinucleating (LHisvMet) B JyA., +
termediates Formed Durin ~~i~n~~Which Species are A%ivaLevina, university ofsydney, Australia Christina Ludwig, University of Sydney,Australia Peter h Lay, University of Sydney,Australia ~~~tat~ione (g-6lu-Cys-Gly, GSH), the most abundant of b~olQ~i~a% ~e~~~ta~~~, is directly involved in cellular metabolism of genotoxic and car~~~oge~i~Cr(V1) OH2--/’ 0%IV& ~~rn~Qu~ds(a comprehensive recent review is given in the references [1,2]). & TI~~~nbatio~of isolated DNA with the Cr(VI) + GSH reaction mixture (but not %$a 7yNp~“Coo” ” roducts of this reaction), as well as exposure of mammalian ad to potentially genotoxic lesions, such as strand breaks and -aoc*‘Ci*bo ~S~“Cr(II~)-D~A adducts [1,2]. We performed the first structural studies of the reactive intermediates, formed during the Cr(VI) + GSH reaction in aqueous solutions, using a combination of X-ray absorption spectroscopy, electrospra~ mass spectrometry, and analytical techniques. Conditions for quantitative generation of Cr(VI)in soiutions have been developed, and the structures of these complexes have been assignedas I a speciesI representsthe first known example of reversible H20 binding to a C %i~era~re, there was no evidence for the formation ofdetectable county of Cr of1 and IXin neutral aqueous solutions have been studied. These data aglowed was tested in the presenceof only one of the intermediates (either I or II). Comple strand breaks in plasmid DNA. Studieswill also be reported on the roles of I and II in the equation Financial support of this work was provided eferences [I] @odd, ; Levina, A.; Lay, P. A. Coord. @hem. [2] Lavina, A.; Codd, ; Dillon, C. T.; Lay, P.A. Progr. Inog. C [3] Levina, A.; Zhang, .; Lay, P.A. Inorg. Chem. 2003,42,7’67 141 Levina, A.; Lay, P. A. To be submitted.

-(lot

OOCyNH3’ --I”2yJ i pp;

q-ix 0 C”W WC3 %$i !!