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Biomedical subjects

F Montero

Publications and source records attributed to F Montero.

At least 37 records · Page 2Linked to original sources
PubMed1995

Interaction with DNA of photoactive viologens based on the 6-(2- pyridinium)phenanthridinium structure.

A new type of DNA-interacting violgens derived from the N,N'-dialkyl 6-(2-pyridinium)-phenanthridinium structure (in which dialkyl is -CH2CH2-,-CH2CH2CH2-, or (-CH3)2) have been synthesized. Electronic spectroscopy, steady-state and time-resolved fluorescence, cyclic voltammetry, binding isotherms, viscosity titrations, and molecular modeling techniques were employed to characterize the structural, photophysical and redox properties of the novel drugs as well as the corresponding drug-DNA complexes. The viologens display significant visible absorption (up to ca. 490 nm), and a rather intense luminescence (phi cm from 0.06 to 0.20 at 491-565 nm wavelength maxima) which is efficiently quenched by DNA. The calculated redox potentials of these drugs in their singlet excited state (+2.1 V vs. SHE) predict a large driving force for a photoelectron transfer reaction from the nucleobases to the drugs. Photochemical measurements of the viologens in the presence of mononucleotides, nucleosides, and deoxyribose indicate that the observed fluorescence quenching occurs indeed by electron transfer from the DNA bases rather than the sugar phosphate backbone. Large association constants to double helical DNA (in the order of 10(5) M-1) have been evaluated from the absorbance-based binding isotherms. Viscosimetry supports intercalation of the drugs into the DNA helix. Computer simulations (molecular mechanics of d(CGCGCG)2-drug complexes) confirm the intercalative nature of the binding and provide finer details about the geometry of the different viologen-DNA complexes. Molecular modeling has also revealed a stereoselective interaction of the enantiomeric drug conformers with the chiral DNA helix. A DNA-targeted drug design of future generations of these ligands in order to improve and/or modulate their photochemical, redox, and nucleic acid binding properties appears to be possible by a careful selection of the N,N'-dialkylating chain and/or the substituents on the azaheterocyclic moieties.

Base Sequence↗
PubMed1994

[Rational use of psychotropic drugs and social communication role].

Extra-clinical factors about the influences affecting the prescription and use of drugs are reviewed. Special attention is given to regulatory agencies, the pharmaceutical industry, and mass media. The problems and public health consequences of the irrational use of drugs are rarely documented in Latin America. Analysis of these factors, information sources, and rational use of psychotropic drugs will require multiple strategies such as social communication and policy formulation to define goals and objectives related to population information, doctors' and individual citizens' decision making processes, and participation of consumers in improving the use of psychotropic drugs.

Advertising↗
PubMed1991

Thermal denaturation profiles of deoxypolynucleotide-destabilizer ligand complexes: semiempirical studies.

In this paper, we study the dependence of the Tm (melting temperature) of complexes formed between double-stranded deoxypolynucleotides and pure destabilizer nonspecific ligands on Kc (intrinsic association constant), nc (apparent site size), and wc (cooperativity constant). Using the Sequence Generating Function (SGF) method, we have found a simple, analytical relationship between the Tm and these interaction parameters. The validity of this relationship depends strongly on the sigma value (sigma being the nucleation parameter of the deoxypolynucleotide). Through the equation so obtained, it is possible to evaluate Kc, nc, and wc from the melting temperature of three experimental thermal denaturation profiles at different r (ligand/deoxypolynucleotide ratio) values. However, when wc greater than 100, a degeneration in the wc and Kc values appears, and the study of the free deoxypolynucleotide region in the melting profile is necessary in order to accurately evaluate these two parameters. The method has been checked using complexes formed with poly(d(A-T].poly(d(A-T] and both bovine pancreatic ribonuclease and protein GP32 of phage T4 as experimental models. The applicability of the method here developed is discussed in relation to the nature of the ligands and the sigma and wc values.

Animals↗
PubMed1991

Cooperative interaction of the C-terminal domain of histone H1 with DNA.

We have studied the interaction of the isolated C-terminal domain of histone H1 with linear DNA using precipitation curves and electron microscopy. The C-terminal domain shows a salt-dependent transition towards cooperative binding, which reaches completion at 60 mM NaCl. At this salt concentration, the C-terminal domain binds to some of the DNA molecules, leaving the rest free. A binding site of 22 base-pairs can be calculated from the stoichiometry of the precipitated fractions. The C-terminal domain condenses the DNA in toroidal particles. The average inner radius of the particles is of the order of 195 A. Consideration of the value of the inner radius of the toroids in the light of counterion condensation theory suggests that in these complexes the isolated C-terminal domain is capable of nearly full electrostatic neutralization of the DNA phosphate charge.

Animals↗
PubMed1991

Study of an error-prone hypercycle formed from two kinetically distinguishable species.

Asymmetry within both the amplification factor values (Ak) and cross-catalytic hypercyclic constant (Kjk) and its influence on the stability of a two-membered error-prone hypercycle has been exhaustively studied from a deterministic point of view and the bifurcation diagram as a function of the quality factor (Q) has been obtained. In the more general case, several Q critical values appear, changing their relative position in the diagram depending on the Ak and Kjk values. The order of the Q critical values affects both the general properties of the system and the stability of the hypercyclic organization. The importance of this asymmetry in the selective and evolutionary properties of the hypercycle is also discussed.

Journal Article↗
PubMed1989

Thermal denaturation profiles of deoxypolynucleotide-ligand complexes: semiempirical studies.

We have semiempirically studied the thermal denaturation profiles of complexes formed between double strand polynucleotides and pure stabilizer nonspecific binding ligands. By using the McGhee model (J. D. McGhee, (1976) Biopolymers 15, 1345-1375) we have found a simple, analytical relationship between the melting temperature (Tm) and the Kh (intrinsic association constant), nh (apparent site size), and wh (cooperativity constant) values of the interaction. The validity of this approach strongly depends on the sigma value (sigma being the nucleation parameter of the DNA). Through the equation so obtained it is possible to calculate the Kh, nh, and wh values from the melting temperature of three experimental thermal denaturation profiles at different r (ligand/polynucleotide ratio) values. The method has been checked by studying the thermal denaturation profiles of daunomycin-poly(d(A-T)).poly(d(A-T)) complexes in two different salt concentrations. The results so obtained are compared with those previously described using other techniques. The applicability of the method here developed is discussed in relation with both the nature of the ligands and the value of the nucleation parameter (sigma).

DNA↗
PubMed1989

Kinetic analysis of psi-DNA structure formation induced by histone H1 and its C-terminal domain.

In this paper we have studied the kinetics of psi-DNA structure formation induced by H1 and H1 peptides containing the C-terminal domain, namely the CTB peptide, obtained by thrombin digestion, and the CNBS peptide, derived from N-bromosuccinimide treatment of H1. The time course for the formation of the psi structure has been followed by measuring the changes in ellipticity at 270 nm as a function of time under different experimental conditions. In all cases studied here, we have observed the existence of two elementary processes: one fast, the other slow. Kinetic experiments performed with high molecular weight DNA showed that the greater the salt concentration, the higher was the apparent rate of psi structure formation. In complexes formed with sonicated DNA and H1, CNBS and CTB, we observed that the greater the content of the C-terminal domain, the higher was the apparent rate at which the final psi structure was reached. Thus, the presence of increasing amounts of either salt or C-terminal domain facilitates the formation of the psi structure. The molecular basis for these phenomena is discussed. The influence of the order of addition of the different components of the complex on the kinetics of psi structure induction is also studied.

Circular Dichroism↗
PubMed1988

Influence of the hypercycle on the error threshold: a stochastic approach.

The role of fluctuations on the error threshold of the hypercycle has been studied by a stochastic approach on a very simplified model. For this model, the master equation was derived and its unique steady state calculated. This state implies the extinction of the system. But the actual time necessary to reach the steady state may be astronomically long whereas for times of experimental interest the system could be near some quasi-stationary states. In order to explore this possibility a Gillespie simulation of the stochastic process has been carried out. These quasi-stationary states correspond to the deterministic steady states of the system. The error threshold shifts towards higher values of the quality factor Q. Moreover, information about the fluctuations around the quasi-stationary states is obtained. The results are discussed in relation to the deterministic states.

Animals↗
PubMed1988

Transition state of the glycolytic pathway under FDP saturating conditions: experimental studies and a theoretical model.

1. The transition state of the glycolytic pathway, under FDP saturating conditions, from no ADP to ADP-saturating levels, is studied in a metabolic model in vitro obtained from rat skeletal muscle. 2. When ADP is absent from the reaction mixture a steady state for NADH concentration is observed. After ADP addition, a new steady state is reached. The transition state from the first steady state to the second one shows a pulse of NADH. Both the profile and the size of this pulse depend on the enzyme concentration. 3. A kinetic model of the lower part of glycolysis (after PFK reaction) is proposed, and this is described by a set of first order coupled nonlinear differential equations. The results obtained through stability analysis and numerical integration of these equations agree with the experimental ones. 4. The possible role of the above mentioned transition state on the transmitter mechanism of glycolytic oscillations from PFK to the lower part of the glycolysis is discussed.

Adenosine Diphosphate↗
PubMed1987

Interactions of the high-mobility-group-like Ceratitis capitata C1 proteins with DNA.

We have studied the interactions of the high-mobility-group-like proteins (C1a1, C1a2 and C1b) from the fruit fly Ceratitis capitata with DNA. Nitrocellulose filter binding assays, thermal denaturation studies and spectrofluorimetry of the complexes revealed the existence of specific and nonspecific interactions. Thermal denaturation curves showed that the three proteins stabilized the DNA, thus suggesting a preferential binding to double-stranded DNA. The calculation of the thermodynamic parameters of the interactions showed that the nonspecific bindings were characterized by low association constants (Ka) with values ranging from 2.7 X 10(4) M-1 to 2.0 X 10(6) M-1. Also, the cooperativity of these interactions was relatively high (cooperativity factor, w, values ranging over 20-35), and the number of nucleotides involved was low (1-3 base pairs). On the other hand, the existence of specific interactions between C1 proteins and DNA was suggested by two facts: the retention of C. capitata [3H]DNA in nitrocellulose filters was only a low percentage of total input DNA and there was a marked size dependence of the binding (25% retention of a 40-kb DNA and only 3% retention with a DNA of 1 kb). The specific bindings had higher Ka values than the nonspecific ones, and they also were cooperative. Some differences were observed between C1b and the C1a proteins about the way they interact with C. capitata DNA.

Animals↗
PubMed1987

Studies on evolutionary and selective properties of hypercycles using a Monte Carlo method.

The most relevant properties of hypercycles were previously studied mainly from a theoretical point of view. We have developed a Monte Carlo method simulating hypercyclic organization to obtain information about the dynamics of this prebiotic organization. Nucleation, growth, and selective properties have been tested and the results obtained are in good agreement with those of the theoretical predictions. The influence of hypercyclic organization on the "error threshold" has also been studied. As a consequence of the emergence of a hypercycle, the value of this threshold decreases. The amount of this decrease depends on the population size. Moreover, for some interval of quality factor values, either the hypercycle organization or an error catastrophe can be produced, depending on the initial conditions. The influence of these phenomena on both the dynamic behavior and evolutionary advantages of the hypercycle, as well as their decisive roles on genome size, are discussed.

Biological Evolution↗
PubMed1987

Influence of carboxyl groups on conformation of histone H1 from Ceratitis capitata.

Salt and pH-dependent effects on the local conformation of the two tyrosine residues of the histone H1 from the fruit fly Ceratitis capitata have been studied by difference spectroscopy, circular dichroism (CD), fluorescence emission and quenching of tyrosine emission by KI. Four different solvent conditions were used: pH 1.0 and pH 6.0 in the presence or absence of 1 M NaCl. The results clearly indicate a partial folding of the fruit fly histone H1 in the absence of NaCl upon pH increasing from 1.0 to 6.0. This folding is achieved only through ionization of acidic side chains which leads to an environment of the tyrosine residues similar to that found in salt-folded histone H1. Furthermore, the present results give new insights into the states of the tyrosine residue responsible for the tyrosinate-like fluorescence emission at 340 nm described previously (Jordano, J., Barbero, J.L., Montero, F. & Franco, L. (1983) J. Biol Chem. 258, 315-320).

Animals↗
PubMed1985

Modification of the lysine residues of histones H1 and H5: effects on structure and on the binding to chromatin.

The extensive modification of histone H1 from calf thymus with the amino-group reagent dimethylmaleic anhydride (over 35 lysine residues modified per molecule) produces no effect on its secondary structure detectable by circular dichroism (far UV). Fluorescence and circular dichroism (near-UV) of the modified histone show variations in the local environment of its sole tyrosine residue. These changes are reversed on regeneration of the modified amino groups. While histone H1 is easily dissociated with this reagent from calf thymus or chicken erythrocyte chromatin, a much stronger treatment is needed to liberate histone H5 from erythrocyte chromatin. This difference appears to be related to the higher arginine content of histone H5.

Animals↗
PubMed1985

Condensation of DNA by the C-terminal domain of histone H1. A circular dichroism study.

The condensation of DNA by the C-terminal domain of histone H1 has been studied by circular dichroism in physiological salt concentration (0.14 M NaF). As the intact H1 molecule, its C-terminal domain induces the so-called psi state of DNA that is characterized by a nonconservative circular dichroism spectrum which is currently attributed to ordered aggregation of the DNA molecules. On a molar basis, intact H1 and its C-terminal domain give spectra of similar intensity. Neither the globular domain of H1 nor an N-terminal fragment, that includes both the globular and N-terminal domains, has any effect on the conservative circular dichroism of DNA. From these results it is concluded that the condensation of DNA mediated by histone H1 is mainly due to its C-terminal domain. The effect of the salt concentration and the size of DNA molecules on the circular dichroism of the complexes are also examined.

Animals↗