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S Weinberger

Publications and source records attributed to S Weinberger.

18 recordsLinked to original sources
PubMed1998

Unknown peptide sequencing using matrix-assisted laser desorption/ionization and in-source decay.

The results of a study to determine the utility of in-source decay fragmentation of matrix-assisted laser-desorbed ions for obtaining useful sequence information on unknown peptides are presented. Six peptides were purified by high-performance liquid chromatography and submitted as single blind unknowns. The in-source decay fragment ion data were collected on a linear time-of-flight mass spectrometer equipped with delayed extraction. These fragment ion data were manually interpreted on the basis of known fragmentation pathways to determine a proposed sequence. The proposed sequences for three of the unknowns were essentially correct, with a few minor errors. A fourth unknown had significant errors associated with its proposed sequence due to misinterpretation of the fragmentation data. Two unknowns were found to have undergone significant sample degradation prior to analysis, which compromised the results for these samples. An example of the use of protein database searching of a partial peptide sequence to aid in a sequence determination is also presented.

Amino Acid Sequence↗
PubMed1992

Attenuation of DNA-protein interactions associated with intrinsic, sequence-dependent DNA curvature.

Inherently curved DNA segments, associated with short runs of adenines, have been identified in many gene regulatory regions, yet their physiological significance remains unknown. The observations reported in this study indicate that intrinsically bent nucleic acid fragments are characterized by substantially attenuated affinities toward DNA-binding proteins involved in structural functions, such as H1 histone and protamine, as well as toward various DNA-modifying enzymes including ligases and exo- and endonucleases. Two mechanisms might be responsible for the altered binding properties. According to the first mechanism, the attenuated binding affinities and the bending represent two independent consequences of the unique structural parameters exhibited by A-tracts. Indeed, analysis of the degradation products obtained upon exposure of the curved sequences to various chemical nucleases points toward the narrowing of the DNA minor groove, a conformational modulation known to characterize A-tracts and to run along the axially-bent motifs, as a potential determinant of the observed binding attenuation. Alternatively, the conformational constraints which result from the stable bending might act to modulate the strength of DNA-protein interactions. Although the factor directly responsible for the altered binding affinities revealed by the bent sequences cannot as yet be conclusively resolved, it is proposed that a reiteration of this specific factor, being either an A-tract or a bend, in phase with the DNA helical repeat acts to amplify the modulation of the binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1992

The advantage of d-sotalol over dl-sotalol in a patient with ventricular arrhythmias and comorbid bronchospasm.

The anti-arrhythmic agent sotalol, a racemic mixture of d- and l-isomers, has inherent beta-adrenoceptor blocking activity due to the l-isomer form. For patients with contraindications to beta-adrenoreceptor blockade, dl-sotalol has potentially untoward effects that may limit its usefulness. The case of a man with resistant life-threatening ventricular arrhythmias who responded favorably to dl-sotalol, but developed worsening of underlying bronchospastic lung disease, is presented. A change in therapy to the d-isomer form of sotalol, d-sotalol, was effective in suppressing his ventricular arrhythmias without further aggravation of bronchospasm.

Bronchial Spasm↗
PubMed1990

Extensive interference of DNA packaging processes affected by chemotherapeutic drugs.

The therapeutic and cytotoxic effects exerted by DNA-binding drugs used for chemotherapy originate from a rather large variety of modifications sustained by the nucleic acids upon interaction with the chemical agents. Notably, these modifications are generally considered as involving the following localized chemical or structural processes: base alkylations, frameshift mutations or strand breakages at specific sites, interstrand cross-links, and local structural transitions within the secondary configurations. We find that antitumor agents hinder or prevent altogether the long range packaging of DNA molecules into compact, ordered states. This effect, observed even at low drug to base pair ratios, is general: it is induced by DNA groove binders as well as by intercalators. Nucleoprotein complexes are found to be efficiently protected against the decondensing effect of the drugs. These observations point toward a generic mechanism for the effectiveness of DNA-binding drugs against tumor cells and viruses as well as for the severe effects of chemotherapy on male fertility: actively dividing systems, such as tumor cells, are characterized by regions of chromatin which are decondensed for the purpose of replication and transcription, and therefore accessible to the drugs. Similarly, both viral infection and spermatogenesis, where histones are replaced by protamines, involve transient formation of relatively uncondensed DNA species and subsequent packaging into extremely tight structures.

Chromomycins↗
PubMed1990

Chiral and structural discrimination in binding of polypeptides with condensed nucleic acid structures.

In biological systems nucleic acids are invariably found in highly compact forms. These rather intricate forms raise questions of basic importance which are related to the various factors involved in the condensation processes, the chemical, physical, and structural features revealed by the packed species, and the effects of the extremely tight packaging upon interactions of the DNA molecules with proteins and drugs. A means for addressing these questions on a molecular level is provided by various procedures known to induce in vitro condensation of DNA molecules into highly compact species which, in turn, may serve as a model for the in vivo physical organization of nucleic acids. A study of the optical properties of the tightly packed DNA molecules indicates that the interactions of these species with polypeptides are characterized by distinct, hitherto unobserved, chiral and structural discrimination. Specifically, the polypeptides found to be selected against are composed of those amino acids that are not normally used in protein biosynthesis, such as D-lysine or ornithine. These findings provide new clues to long debated topics such as the specific universal chirality of amino acids in proteins or the correlation between conformational flexibility of polypeptides and their ability to form stable compact complexes with nucleic acids.

Chemical Phenomena↗
PubMed1990

A unique binding cavity for divalent cations in the DNA-metal-chromomycin A3 complex.

Binding of chromomycin A3 (CRA) to calf thymus DNA was investigated in the presence of divalent cations using visible absorption and 1H-nmr spectroscopies. An apparent equilibrium binding constant (approximately 10(11) M-1) was obtained from metal competition experiments using EDTA to remove the metal cation from the DNA-M-CRA (M: metal) complex. The large binding constant of the drug to DNA enabled us to obtain essentially complete complexation of CRA to the short homogeneous d(ATGCAT)2 duplex using stoichiometric amounts of the metal cation. Large induced chemical shifts were observed in the 1H-nmr spectrum of the above complex using the paramagnetic Co2+ cation, indicating that the metal occupies a unique binding site. Since no induced 1H-nmr chemical shifts were observed for the drug-Co2+ mixture, it was concluded that no metal-drug complex is formed. In addition, it was found that bound CRA is negatively charged at physiological pH and binding to the DNA could be affected only by using metal cations whose ionic radius size (less than 0.85 A) and charge (2+) were simultaneously satisfied. Stringent metal cation selectivity for the DNA-M-CRA complex may be intimately connected with the antitumor selectivity of CRA, since different types of cells generally possess widely differing molar concentrations of metal cations.

Animals↗
PubMed1988

Homotopy invariance of eta-invariants.

Intersection homology and results related to the higher signature problem are applied to show that certain combinations of eta-invariants of the signature operator are homotopy invariant in various circumstances.

Journal Article↗
PubMed1986

Characterization of Escherichia coli mutant strains deficient in AP DNA-repair synthesis.

Deficiency of apurinic/apyrimidinic (AP) DNA-repair enzymes in crude extracts of E. coli mutants was determined by following general and specific AP DNA-repair synthesis via nick translation in the presence of either all four dNTPs, or only one dNTP. We have shown that mutations either in DNA polymerase I or in AP endonucleases or in both, inhibit to different degrees the ability to repair AP DNA. The polA mutation totally abolishes the ability to perform both general and specific AP DNA repair, while the polAex mutation affects only general AP DNA repair. The xthA tight mutants, including the deletion mutant BW9101, can cope with small amounts of AP sites but hardly with high amounts of these lesions. In addition we have found that crude extracts of the xthA mutants degrade AP DNA by two modes: a nonspecific, and an AP-specific mode. These phenomena are common to all xth mutants and enabled us to discover this mutation. In contrast to the xth mutants so far isolated, BW2001 exhibits marked sensitivity to MMS and to X-ray irradiation. We found that this strain has a proficient DNA polymerase I but is absolutely deficient in AP endonucleases. We attribute its sensitivities to a secondary mutation at the structural gene of endonuclease IV.

Apurinic Acid↗
PubMed1985

Group actions and higher signatures.

Let pi be a nontrivial finite group and M be a closed manifold. An interesting question is whether or not M has the R-homology type of a manifold admitting a free pi action. Here this problem is studied for actions that are "homologically trivial." If pi(1)M is nontrivial these questions are intimately related to the Novikov higher signature conjecture, but the results are new even in the simply connected case.

Journal Article↗
PubMed1983

Postincision steps of photoproduct removal in a mutant of Bacillus cereus 569 that produces UV-sensitive spores.

An excision-defective mutant of Bacillus cereus 569 is normal in incision and repair synthesis, but rejoining of incision breaks is defective, resulting in accumulation of low-molecular-weight DNA after UV irradiation. The defect in removal of photoproducts by exonuclease after incision renders both vegetative cells and dormant spores of the mutant sensitive to UV. A similarity is indicated to the uvrD mutation described recently in Escherichia coli.

Bacillus cereus↗