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J C Chottard

Publications and source records attributed to J C Chottard.

36 records · Page 2Linked to original sources
PubMed1986

A high melting cis-[Pt(NH3)2[d(GpG)]]adduct of a decanucleotide duplex.

The [cis-Pt(NH3)2(d(GCCGGATCGC)-N7(4), N7(5))]-d(GCGATCCGGC) duplex has been prepared with Tm = 49 degrees C (vs 58 degrees C for the unplatinated form). NMR of the ten observable imino protons supports a kinked structure with intact base pairing of the duplex on the 3'-side of the d(GpG).cis-Pt chelate (relative to the platinated strand) The modification of the B-DNA type CD spectrum, due to the platinum chelate, is comparable to that observed for the platination (at a 0.05 Pt:base ratio) of the Micrococcus Lysodeikticus DNA (72% GC).

Base Sequence↗
PubMed1984

DNA fragment conformations. A 1H-NMR conformational analysis of the d(G-G)-chelated platinum-oligonucleotide d(A-T-G-G)cisPt.

The conformation of d(A-T-G-G) and d(A-T-G-G)cisPt has been investigated by 1H-NMR at 500 MHz and 90 MHz under various experimental conditions of temperature and concentration. Analysis of the coupling constants between the deoxyribose protons shows that all the sugar rings of d(A-T-G-G) adopt the S(C2'-endo) conformation most of the time. By contrast, in the platinated tetramer, d(A-T-G-G)cisPt, the N(C3'-endo) conformation is highly predominant for the internal dG residue while the S(C2'-endo) conformation is largely favoured for the other residues as in the case of the unplatinated compound. The relaxation time and nuclear Overhauser effect measurements indicate that the orientation of the two guanines of d(A-T-G-G)cisPt is anti in agreement with the previous results obtained for the dimers: r(G-G)cisPt, d(G-G)cisPt. On lowering the temperature from 80 degrees C to 20 degrees C, several proton resonances of d(A-T-G-G)cisPt exhibit large chemical shift and linewidth variations. The most spectacular temperature effect was observed for the internal dG(H1') and dT(H4') protons. All the delta = f(t) curves display a sigmoid form with the same mid-point temperature of 44 +/- 2 degrees C. This mid-point temperature together with the observed chemical shift and linewidth variations were found to be independent of the d(A-T-G-G)cisPt concentration. These results suggest that d(A-T-G-G)cisPt can adopt two different conformations depending on the temperature. The enthalpy for the transition between the high and low temperature conformations is about 84 kJ/mol.

Cisplatin↗
PubMed1982

Conformational analysis of the adduct cis-[Pt(NH3)2 d(GpG)]+ in aqueous solution. A high field (500-300 MHz) nuclear magnetic resonance investigation.

A 500, 400 and 300 MHz proton NMR study of the reaction product of cis-Pt(NH3)2Cl2 or cis-[Pt(NH3)2 (H2O)2] (NO3)2 with the deoxydinucleotide d(GpG): cis-[Pt(NH3)2 d(GpG)] was carried out. Complete assignment of the proton resonances by decoupling experiments and computer simulation of the high field part of the spectrum yield proton-proton and proton-phosphorus coupling constants of high precision. Analysis of these coupling constants reveal a 100% N (C3'-endo) conformation for the deoxyribose ring at the 5'-terminal part of the chelated d(GpG) moiety. In contrast, the 3'-terminal -pG part of the molecule displays the normal behaviour for deoxyriboses: the sugar ring prefers to adopt an S (C2'-endo) conformation (about 70%). Extrapolating from this model compound, it is suggested that Pt chelation by a -dGpdG- sequence of DNA would require a S to N conformational change of one deoxyribose moiety as the main conformational alteration and lead to a kink in one strand of the double-helical structure of DNA.

Chemical Phenomena↗
PubMed1982

Interaction of cis-[Pt(NH3)2(H2O)2](NO3)2 with ribose deoxyribose diguanosine phosphates.

The three diguanosine phosphates GpG (4 X 10(-4) M), d(GpG) (10(-5) M), and d(pGpG) (10(-5) M) have been reacted with cis-[Pt(NH3)2(H2O)2](NO3)2 (1 Pt/dinucleotide) in water at pH 5.5 and 37 degrees C. In each case a single product is formed. The three complexes have been characterized by proton nuclear magnetic resonance (1H NMR) and circular dichroism (CD) analyses. They are N(7)-N(7) chelates of the metal with an anti-anti configuration of the bases. They present a conformational change upon deprotonation of guanine N(1)H whose pKa is ca. 8.7 (D2O). Their CD spectra, compared to those of the free dinucleotides, exhibit an increase of ellipticity in the 275-nm region, which can be qualitatively related to the characteristic increase reported for platinated DNA and poly(dG) . poly(dC). These results are in favor of the hypothesis of intrastrand cross-linking of adjacent guanines, by the cis-PtII(NH3)2 moiety, after a local denaturation of DNA.

Chemical Phenomena↗
PubMed1978

Formation of complexes between microsomal cytochrome P-450-Fe(II) and nitrosoarenes obtained by oxidation of arylhydroxylamines or reduction of nitroarenes in situ.

A cytochrome P-450 complex exhibiting a Soret peak at 454 nm is formed by direct interaction of nitrosobenzene with NADPH-reduced rat liver microsomes in anaerobic conditions, by reaction of phenylhydroxylamine with aerobic microsomes or during nitrobenzene reduction by NADPH-reduced or dithionite-reduced microsomes. In the latter conditions, the complex formation is only transient as it is unstable to dithionite. Analogous reactions with myoglobin lead to the previously described myoglobin-Fe(II)-nitrosobenzene complex which has similar properties to those of the 454-nm-absorbing cytochrome P-450 complex. This analogy, together with the various conditions of its formation, strongly indicates that it is a cytochrome-P-450-Fe(II)-nitrosobenzene complex. The corresponding complex with the 4-chloro-nitrosobenzene ligand is formed in similar conditions. Cytochrome P-450-Fe(II) complexes with nitrosoarenes seem less stable than the previously described complexes with nitrosoalkanes.

Animals↗
PubMed1977

Nitrosoalkanes as Fe(II) ligands in the 455-nm-absorbing cytochrome P-450 complexes formed from nitroalkanes in reducing conditions.

Primary and secondary aliphatic nitroalkanes RR'CHNO2, react with microsomal cytochrome p-450 in the presence of dithionite leading to new complexes with a Soret peak at 455 nm. The formation of these complexes is inhibited completely by CO and partially by metyrapone. However, once formed, their exogenous ligand is not displaced by excess CO. By deoxycholate treatment they are transformed into 423-nm-absorbing cytochrome P-420 complexes, which are spectrally similar to the corresponding RR'CHNO2-derived myoglobin complexes. The 455-nm-absorbing complexes are equally produced from RR'CHNO2 reduction, microsomal NADPH-dependent oxidation of the corresponding hydroxylamine RR'CHNHOH, or interaction of the nitrosodimer (RR'CHNO)2 with reduced cytochrome P-450. All the reported results are consistent with the involvement of a new class of ligands of cytochrome P-450-Fe(II), which are the unstable aliphatic nitrosomonomers RR'CHNO, whose nitroso group is isoelectronic with dioxygen and whose stabilisation results from their strong binding to heme-Fe(II), thus explaining the observed inhibition of the hydroxylating function of cytochrome P-450.

Alkanes↗
PubMed1977

Nitrosoalkanes as Fe(II) ligands in the hemoglobin and myoglobin complexes formed from nitroalkanes in reducing conditions.

Primary and secondary aliphatic nitro compounds, R2CHNO2, react with myoglobin and hemoglobin, in the presence of sodium dithionite, leading to new complexes with Soret peaks respectively at 425 and 421 nm. These complexes are very stable even after disappearance of the starting nitro compounds and do not exchange their exogenous ligand after 10 h under 1 atm (101 325 Pa) CO. They are low-spin hexacoordinated myoglobin or hemoglobin complexes, as shown by the resonance Raman spectrum of the nitromethane-derived human hemoglobin complex which is similar to those of the known hemoglobin complexes with O2, CO, NO and nitrosobenzene. Evidence has been produced to show that the nitro compounds themselves do not bind to the hemoproteins; we propose that among the reduction derivatives produced in situ by dithionite, the corresponding unstable nitroso monomers, whose nitroso group is isoelectronic with dioxygen, are the actual ligands of the 425-nm or 421-nm-absorbing complexes.

Alkanes↗
PubMed1976

[Modality of the antimitotic acitivity of the diamine cis-dichloroplatinum (II) studied on the plant cell].

In the order of decreasing doses, cis-platinum (II) diamine dichloride acting on root meristem of Allium sativum produces first an irreversible metostatic effect quickly followed by lethal effect, then a variable mitodepression accompanied by important chromosomal alterations: numerous disruptions and stickiness. This chromatoclasic effect persists at very low concentrations but stathmodieretic effect is not observed. The chromatoclasic activity of the compound is compared to that of other antitumoral drugs.

Cisplatin↗