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S Pavlopoulos

Publications and source records attributed to S Pavlopoulos.

23 records · Page 2Linked to original sources
PubMed1996

Structural characterization of the 1:1 adduct formed between the antitumor antibiotic hedamycin and the oligonucleotide duplex d(CACGTG)2 by 2D NMR spectroscopy.

2D NMR spectroscopic methods have been used to determine the structure of the adduct formed between the antitumor antibiotic hedamycin and the oligodeoxyribonucleotide duplex d(CACGTG)2. Evidence for both intercalation and alkylation in the adduct was observed, and a model for the binding interaction was constructed based on intermolecular NOEs and distance-restrained molecular dynamics. In our computationally refined model, the anthrapyrantrione chromophore of hedamycin is intercalated between the 5'-CG-3' bases with the two aminosugar groups placed in the minor groove and the six carbon bisepoxide side chain located in the major groove. The anglosamine sugar attached at C8 is oriented in the 3' direction relative to the intercalation site, while the N,N-dimethylvancosamine attached at C10 is oriented to the 5' side, with each aminosugar wedged between a guanine exocyclic amino group and one of the groove walls. The terminal epoxide carbon C18 is covalently bound to the N7 atom of the central guanine, as evidenced by lability of the C8 hydrogen of this purine upon reaction with hedamycin. Our binding model places the C10-attached N,N-dimethylvancosamine of hedamycin in van der Waals contact with the alkylated strand. A strong NOE contact verifies the close proximity of the terminal methyl group (C19) of the bisepoxide side chain to the methyl group of the thymine on the 3' side of the alkylated guanine. This, in conjunction with other data, suggests hydrophobic interactions between the bisepoxide chain and the floor of the major groove may contribute to sequence recognition. Furthermore, it is proposed that the 5'-CGT sequence selectivity of hedamycin arises, in part, from complementarity in shape between the chromophore substituents and the major and minor groove at the binding site.

Alkylation↗
PubMed1995

A 1H NMR analysis of the interaction between terephthalamide derivatives and the oligonucleotide duplex d(GGTAATTACC)2.

A series of terephthalamide derivatives with the substituents R = NO2, NH2 and NHCOCH2NH2 on the central aryl ring have been synthesized, and their interaction with the DNA decamer d(GGTAATTACC)2 has been studied by 1H NMR. The amine and nitro (R = NH2, NO2) derivatives bind with micromolar affinities and exhibit NMR spectra characteristic of fast exchange on the chemical shift time scale. The glycine derivative (R = NHCOCH2NH2) binds more tightly and a number of its resonances are in intermediate to slow exchange on the chemical shift time scale. Estimates of binding affinities and bound chemical shifts of ligand and DNA resonances were made from an analysis of chemical shifts and linewidths in a series of spectra with ligand duplex mole ratios ranging from 0:1 to 2:1. The data unequivocally suggest that all three ligands bind in the minor groove of the DNA decamer and more specifically that the binding site is localized over the ATTA sequence. The ligand is able to exchange rapidly between two symmetry-related ATTA sites per decamer.

Amides↗
PubMed1991

A PC data-base with analytical applications for evoked potentials.

Visual Evoked Potentials (VEPs) are gaining ground in the research for diagnosis of neurological disorders and visual defects, as a non-invasive diagnostic tool. Yet, the methods used towards these goals are not universal and far from able to provide a common ground among researchers in collecting, analyzing and comparing their results. This paper is an attempt to close the gap. We have developed a PC data-base and a set of analysis programs with graphic capabilities, frequency analysis, as well as an objective way of describing the signals obtained during VEP experiments.

Database Management Systems↗
PubMedDate not supplied

Characterization of the sequential non-covalent and covalent interactions of the antitumour antibiotic hedamycin with double stranded DNA by NMR spectroscopy.

Hedamycin, a member of the pluramycin class of antitumour antibiotics, consists of a planar anthrapyrantrione chromophore to which is attached two aminosugar rings at one end and a bisepoxide-containing sidechain at the other end. Binding to double-stranded DNA is known to involve both reversible and non-reversible modes of interaction. As a part of studies directed towards elucidating the structural basis for the observed 5'-pyGT-3' sequence selectivity of hedamycin, we conducted one-dimensional NMR titration experiments at low temperature using the hexadeoxyribonucleotide duplexes d(CACGTG)(2) and d(CGTACG)(2). Spectral changes which occurred during these titrations are consistent with hedamycin initially forming a reversible complex in slow exchange on the NMR timescale and binding through intercalation of the chromophore. Monitoring of this reversible complex over a period of hours revealed a second type of spectral change which corresponds with formation of a non-reversible complex.

Alkylating Agents↗