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L A Marky

Publications and source records attributed to L A Marky.

50 records · Page 3Linked to original sources
PubMed1983

Thermodynamics of drug-DNA interactions.

Batch calorimetry, differential scanning calorimetry (DSC), uv/vis absorption spectroscopy, fluorescence spectroscopy, and circular dichroism (CD), have been used to detect, monitor, and thermodynamically characterize the binding of daunomycin, dipyrandenium, dipyrandium, and netropsin to poly d(AT) and actinomycin D to salmon testes (ST) DNA. The following thermodynamic binding profiles have been obtained. (table; see text) All the poly d(AT) binding studies were done at 25 degrees C while actinomycin binding to ST DNA was performed at 1 degree C to enhance drug solubility. These thermodynamic parameters are interpreted in terms of specific interactions that have been proposed as part of models for the binding of each drug.

Animals↗
PubMed1982

Synthesis and physical characterization of the self-complementary, alternating pyrimidine/purine hexanucleotide d[CGTACG].

The hexanucleotide d(CGTACG) has been synthesized by a phosphotriester method in which, for the first time, an O-6 protected deoxyguanosine derivative has been used to avoid side reactions of the guanine residues. Conformational analysis by circular dichroism shows that d(CGTACG) maintains a B form under conditions (5 M NaCl) where the all C/G hexanucleotide d(CG)3 adopts a Z form, even though d(CGTACG) is a fully alternating pyrimidine/purine molecular. The delta H for the helix-to-coil transition has been measured.

Base Sequence↗
PubMed1982

The influence of the purine 2-amino group on DNA conformation and stability. Synthesis and conformational analysis of d[T(2-aminoA)]3.

A self-complementary hexanucleotide consisting of thymidine and 2-amino-deoxyadenosine, d(TA')3, has been synthesized by a solid phase phosphotriester method. Melting studies show that the additional hydrogen bond afforded by the 2-amino group substantially stabilizes the duplex. Moreover, conformational analysis using circular dichroism shows that a salt-induced conformational transition occurs, similar to the B leads to Z transition observed for d(CG)n oligonucleotides.

DNA↗
PubMed1981

Thermodynamics of (dG--dC)3 double-helix formation in water and deuterium oxide.

The thermodynamics of double-helix formation by (dG-dC)3 in H2O and D2O were measured spectrophotometrically and calorimetrically. Spectrophotometric values based on plots of inverse melting temperature vs. log of concentration are in good agreement with calorimetry. However, spectrophotometric values based on the shape of absorbance vs. temperature curves are in good agreement with calorimetry only if linear pre- and posttransition base lines are subtracted before analysis. The averages of the enthalpies measured by the three most reliable spectroscopic methods are -56.9 and -62.7 kcal/mol of helix in H2O and D2O, respectively. The corresponding calorimetric values are -59.6 and -65.8 kcal/mol of helix.

Calorimetry, Differential Scanning↗
PubMed1981

Solvent effects on the kinetics and thermodynamics of stacking in poly(cytidylic acid).

The Raman laser temperature-jump technique has been used to measure the kinetics of the coil to helix reaction of poly(cytidylic acid) [poly(C)] in aqueous cosolvent mixtures. The rate of helix formation has a low activation energy and is proportional to reciprocal solvent viscosity. The observations suggest helix formation is rotationally diffusion controlled. The rate of coil formation in poly(C) has an activation energy of approximately 11 kcal/mol, presumably reflecting the electronic stacking interactions which stabilize the helix. Viscous cosolvents, glycerol or sucrose, slow down the rate of coil formation; acetonitrile and formamide at 5 mol % increase the rate relative to that in water. The polar cosolvents may specifically attack a cytosine stack. The absorbance vs. temperature profiles for poly(C) are analyzed with the one-dimensional Ising model. When only optical data are used, the cooperativity parameter, sigma, and the enthalpy, delta H, cannot be uniquely determined. A method is proposed that allows determination of sigma by combining spectroscopic and calorimetric data. The values of sigma derived for poly(C) are between 0.8 and 1.0, and delta H is about -9 kcal/mol of stack. An alternative method using integration of the excess heat capacity curve and extrapolation to fully stacked and random coil species yields a delta H of -7 kcal/mol of stack.

Acetonitriles↗
PubMed1981

Effect of tetramethylammonium ion on the helix-to-coil transition of poly(deoxyadenylylthymidine): a nuclear magnetic resonance and calorimetric investigation.

Differential scanning calorimetry, temperature-dependent NMR, and UV spectroscopy are used to investigate the helix-to-coil transition of poly(deoxyadenylylthymidine) [poly(dA-dT)] in 1 M NaCl and 1 M Me4NCl (tetramethylammonium chloride). All three methods reveal that the polymer has a melting temperature, tm, that is approximately 6 degree C higher in 1 M Me4NCl than in 1 M NaCl. The NMR data show that this increased stability does not result from fundamental changes in base stacking or base pairing in going from 1 M NaCl to 1 M Me4NCl. Consistent with this observation, the calorimetric measurements yield essentially equal enthalpies for the helix-to-coil transition under the two salt conditions (6.8 kcal per base pair in 1 M NaCl and 7.0 kcal per base pair in M Me4NCl). Analysis of the shapes of the calorimetric curves shows that the transition is more cooperative in Me4NCl than in NaCl. Comparison of the calorimetric and van't Hoff enthalpies allows specification of the size of the cooperative unit: 27 base pairs in 1 M NaCl and 32 base pairs in 1 M Me4NCl. The NMR data reveal that the major Me4NCl-induced structural alterations (relative to NaCl) are a change in one glycosidic torison angle and a partial resolution of the two phosphates. The calorimetric experiments indicate that in the absence of fortuitous compensation these conformational changes are not accompanied by a significant enthalpy effect. On the basis of these data, we suggest that in 1 M NaCl poly(dA-dT) assumes predominantly a B-DNA-like conformation where the symmetry repeat occurs every base pair. By contrast, in 1 M Me4NCl the predominant conformation exhibits a dinucleotide repeat consistent with a right-handed alternating B-DNA structure.

Calorimetry, Differential Scanning↗
PubMed1981

Calorimetric and spectroscopic investigation of the helix-to-coil transition of the self-complementary deoxyribonucleotide ATGCAT.

Differential scanning calorimetry and temperature-dependent uv spectroscopy are used to thermodynamically characterize the double-strand to single-strand transition of the self-complementary deoxyribo-oligonucleotide ATGCAT. The calorimetric experiments provide a value of 33.6 kcal (mol of double strand)-1 for the transition between 10 and 90 degree C. In conjunction with available temperature-dependent nmr data (which reveals terminal base pair fraying), we attempt to define specifically those interactions to which the calorimetrically measured enthalpy change refers. Values of delta HV.H. (van 't Hoff enthalpy change) are derived from the spectroscopic and calorimetric data and compared with the delta H obtained directly from the calorimetric experiment. This comparison reveals that the part of the thermally-induced transition that occurs between 10 and 90 degree C is well represented by a two-state process. It is noted that is assessing the applicability of the two-state model it is best to compare the delta with delta HV.H. Hcal. obtained from the calorimetric rather than the spectroscopic data.

Calorimetry, Differential Scanning↗
PubMedDate not supplied

[Volume effect and change in compressibility in intercalation of ethidium bromide and daunomycin in DNA].

A combination of high-precision and density techniques was used to investigate the binding of ethidium bromide and daunomycin to DNA. It was shown that intercalation is accompanied by a decrease in apparent volume and adiabatic compressibility of DNA, which were -28 cm3mol-1 and -20.10(-4) cm3mol-1bar-1 for binding of ethidium to DNA, and -28 cm3mol-1 and -18.10(-4) cm3mol-1bar-1 for daunomycin, respectively. The values obtained have been compared with those of the hydration contributions of atomic groups to the apparent molar volume and apparent molar compressibility of the ligands as well as the contribution of intrinsic compressibility of DNA. The volume effects in the intercalation of ligands correspond to the values expected for the dehydration of aromatic heterocyclic rings. On other hand, negative compressibility changes may be explained by a decrease of the intrinsic compressibility of DNA and possible increase of its hydration as result of conformational changes upon ligand binding.

Antibiotics, Antineoplastic↗