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Biomedical subjects

L G Marzilli

Publications and source records attributed to L G Marzilli.

At least 55 records · Page 3Linked to original sources
PubMed1984

Evidence for similar structural changes on binding of platinum anti-tumor agents to DNA and nucleosomes.

The influence of Pt(II) compounds on the 31P NMR spectra of natural DNA, synthetic polynucleotides, and nucleosomes was investigated. With Pt complexes which are anti-tumor agents, a new peak or shoulder centered at approximately 1.2 ppm downfield from the untreated DNA signal was observed. When Pt compounds known not to be anti-tumor agents were studied, no such new signal was observed. The most reasonable explanation for the downfield resonance is that it is a consequence of a structural change induced in the DNA by the anti-tumor agent. Since the effect of the Pt compounds on nucleosomes was similar, the same structural change is probably occurring in DNA in solution and in nucleosomes. A nonalternating dG . dC polymer, but not alternating G . C or any A . T polymers, exhibited a similar spectral change and this finding suggests that the structural change in the DNA arises primarily from reaction of Pt anti-tumor agents with adjacent G residues.

Animals↗
PubMed1983

31P NMR and viscometric studies of the interaction of meso-tetra(4-N-methylpyridyl) porphine and its Ni(II) and Zn(II) derivatives with DNA.

The interactions of meso-tetra(4-N-methylpyridyl) porphine (TMPyP) and its Zn(II) and Ni(II) derivatives with DNA have been investigated by 31P NMR and viscometric titrations. TMPyP and its Ni derivative increase the viscosity of linear DNA, cause unwinding and reverse coiling of superhelical DNA, and induce a separate downfield peak in the 31P NMR spectrum of DNA. The Zn derivative slightly decreases the viscosity of linear DNA, does not unwind superhelical DNA, and does not give a downfield NMR peak. The main DNA 31P NMR signal is shifted slightly upfield on either the addition of TMPyP or the Ni compound. These results indicate that TMPyP and the Ni(II), but not the Zn(II), derivative bind to DNA by intercalation.

Animals↗
PubMed1981

Electrophoretic determination of charge on carrier-free 99mTc-labeled complexes.

A new method for determining the charge on carrier-free 99mTc-labeled complexes is described. This method and mixed-ligand experiments were used to determine if the charge on the technetium 99m complex of N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (I) is - 1 and if the ligand to technetium ratio in the complex is 2:1. The preparation of an iodinated analog (II) of I and its 99mTc-labeled complex is described, as is the biodistribution of the 99mTc-labeled complex in mice. The synthesis of the 51Cr(III)- and 57Co(III)-labeled complexes also are described. The net biliary excretion in mice of both the 99mTc- and 51Cr-labeled complexes of II was significantly greater than that of the 99mTc-labeled complex of I.

Animals↗
PubMed1981

Radiolabeled benzoylcholine derivatives as possible myocardial-imaging agents.

Two radioiodinated analogs of benzoylcholine were investigated as possible myocardial-imaging agents. O-([2-125I]Iodobenzoyl)-choline and N-([2-125I]iodobenzoyl)cholamine were prepared by nucleophilic substitution of sodium [125I]iodide for stable iodine in O-(N,N]dimethylaminoethyl)-2-iodobenzoate and N-(N',N'-dimethylaminoethyl)-2-iodobenzamide, respectively, and by methylation with methyl iodide. The in vivo distribution of each compound in mice was determined as a function of time. Favorable heart-to-blood and heart-to-lung ratios were obtained with N-([2-125I]iodobenzoyl)cholamine.

Animals↗
PubMed1981

Platinum interactions with nucleic acids: insights from model compounds.

A systematic review of the molecular structures of a large number of platinum(II) complexes with purine and pyrimidine bases and their nucleosides and nucleotides is presented. From these studies it is evident that the endocyclic nitrogen donor atoms of the heterocyclic purine and pyrimidine bases are dominant metal binding sites for Pt(II). Secondary interactions involving the exocyclic functional groups of the bases and the phosphate moiety of nucleotides are also noted. For Pt(II) complexes containing two adjacent (cis) bases, it is further indicated that intracomplex and intercomplex base-base interactions are of particular importance, giving rise in some cases to discontinuous helical arrays of Pt(II) complexes. These helical arrays may provide some insights into platinized-DNA polymers. Attention is also given to polynuclear species which are models for the family of mixed-valent platinum-pyrimidine blues. Finally, an attempt is made to extend the results of small molecule studies to give insights into the general area of Pt(II)-DNA chemistry and, in particular, the mode of action of the active anti-neoplastic agent cisPt.

Binding Sites↗
PubMed1980

4-[125I] iodophenyltrimethylammonium ion, an iodinated acetylcholinesterase inhibitor with potential as a myocardial imaging agent.

4-[125I]Iodophenyltrimethylammonium acetate (4-I-125 PTMA) was prepared by chloramine-T iodination of N,N-dimethylaniline and subsequent methylation with methyliodide. Purification by thin layer chromatography afforded a product whose specific activity approached the theoretical carrier-free level. Biodistribution studies in normal ICR mice showed a significant accumulation of 4-I-125 PTMA in the heart tissue, with heart-to-blood ratios of 12.5, 10.4, 7.8, 3.4, 3.4, and 3.3 at 1, 5, 10, 30, 60, and 120 min, respectively. Initial uptake in the heart was greater than 26% of the injected dose per gram. Twenty-five percent of the activity was excreted unchanged by the kidneys during the first 5 min. Less than half of the injected activity was retained in mice at 120 min.

Animals↗
PubMed1979

A new electrophoretic method for determining ligand: technetium stoichiometry in carrier free 99mTc-radiopharmaceuticals.

An electrophoretic procedure is outlined for the determination of the number of ligands bound to technetium-99m radiopharmaceuticals. The approach involves use of ligands that will complex technetium in a similar fashion but that differ in charge. This approach was applied experimentally to dimercapto ligands in which the ligating sulfur atoms are separated by a flexible three-carbon chain (1,3-dimercapto compounds). Two such ligands studied are 1,3-dimercaptopropane (DMP) and dihydrothioctic acid (DHTA). The Tc compound of DHTA migrates much farther on electrophoresis than the Tc complex of DMP. However, when TcO4- is reduced by SnCl2 or NaBH4 in the presence of equimolar quantities of DHTA and DMP, a new compound is formed being twice as abundant as either the TcDMP or the TcDHTA compound and migrating an intermediate distance. The formation of this new complex and the 1:2:1 distribution indicates that two 1,3-dimercapto compounds are attached to the Tc-center in all three compounds.

Chemical Phenomena↗
PubMed1978

Osmium-labeled polynucleotides: reaction of osmium tetraoxide, with poly-1,N6-ethenoadenylic acid.

Osmium tetraoxide, in the presence of ligands such as pyridine and bipyridine, adds across the etheno bridge of 1,N6-etheno-9-methyladenine and poly-1,N6-ethenoadenylic acid. The Os:P ratio in the labeled polynucleotide was approximately equal to 1 when bipyridine was used as the stabilizing ligand. A similar study with polycytidylic acid, which had been partially modified with chloroacetaldehyde so that some bases were converted to 3,N4-ethenocytosine, gave an OS:P ratio of approximately equal to 1.3. Calf-thymus DNA, in which the adenine and cytosine bases were modified by chloroacetaldehyde, gave an Os:P ratio of approximately equal to 1 after 24 h. These results suggest that 3,N4-ethenocytosine will add two Os labels.

Adenosine Triphosphate↗
PubMed1977

Osmium-labeled polynucleotides. The reaction of osmium tetroxide with deoxyribonucleic acid and synthetic polynucleotides in the presence of tertiary nitrogen donor ligands.

Osmium tetroxide in the presence of pyridine or 2,2'-bipyridine has been found to react completely with the pyrimidine moieties (thymine, uracil, and cytosine) in polynucleotides. Pyrimidine osmate ester moieties, L2OSO4-pyrimidine, were formed. The OSO4 has added across the 5,6 double bond and L=pyridine or 1/2-bipyridine. The pyridine derivatives were not stable and decomposed slowly after the OSO4-pyridine reagent was removed by gel chromatography. Labeled poly(uridylic acid) lost osmium completely during gel chromatography unless the eluent contained a high concentration of pyridine. The products formed between OSO4-bipyridine and polynucleotides were much more stable and the OS label was retained during and after gel chromatography. Both the OSO4-pyridine and OSO4-bipyridine reagents reacted more rapidly than the OSO4-CN-reagent.

Binding Sites↗
PubMed1976

Conformational properties of the osmium tetraoxide bispyridine ester of 1-methylthymine and a comment on the linearity of the trans O=Os=O group.

The preparation and crystal and molecular structure of the osmium tetraoxide bispyridine ester of 1-methylthymine are reported. The complex crystallizes in the triclinic system, space group P1, with a = 11.493(6)A, b = 16.655(7)A, c = 6.082(2)A, alpha = 92.07(3) degrees, beta = 90.58(3) degrees, gamma = 71.36(4) degrees, V = 1102.4 A3, Dm = 1.85(1) g cm-3, DC = 1.84 g cm-3. The unit cell contains 2 osmium tetraoxide bispyridine esters of 1-methylthymine, 2 waters of crystallization and 1 disordered pyridine of solvation. Intensities for 3814 independent reflections were collected by counter methods. The structure was solved by standard heavy-atom techniques and has been refined by full-matrix least squares, based on F, to a final R value of 0.065. The osmium complex binds as a cis osmate ester to the C(5)-C(6) bond of the methylated pyrimidine in a fashion which is expected to be similar to the binding of the complex to thymidine residues in nucleic acids. The conformation of the 1-methylthymine ester is that of a half chair with C(6) showing a substantial deviation, 0.55 A, from the best mean plane of the thymine moiety. The primary coordination sphere about the Os(VI) atom is completed by 2 axial Os=O bonds and the binding of the 2 pyridine ligands in cis positions in the equatorial plane containing the ester linkages. The O=Os=O group is substantially nonlinear, 164.0(5) degrees, and this nonlinearity is attributed to intracomplex electronic effects.

Molecular Conformation↗