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Biomedical subjects

C Marck

Publications and source records attributed to C Marck.

30 records · Page 2Linked to original sources
PubMed1982

Specific interaction of netropsin, distamycin-3 and analogs with LC duplexes: reversion towards the B form of the 2'-deoxy-.2'-deoxy-2'-fluoro-hybrid duplexes upon specific interaction with netropsin, distamycin-3 and analogs.

Binding of the B-form specific ligands netropsin and distamycin-3, -4 and -5 has been used to monitor the presence and/or the inducibility of a B-type structure in various poly-inosinic.poly-cytidilic double stranded polymers with deoxyribose, ribose or 2'-deoxy-2'-fluororibose as sugar on either strand. The efficiency of binding was followed by circular dichroism and further evaluated by the increase in melting temperature of the complexes. The efficient binding of netropsin and distamycins to the hybrid polymer (dIfl)n. (dC)n demonstrated that the fluorine carrying strand may undergo a A to B-type transition reflecting a change of the 2'-deoxy-2'-fluororibose from the 3'-endo to the 1'-exo or 2'-endo pucker. The less efficient binding of the same ligands to the reverse hybrid (dI)n.(dCfl)n showed that the geometry of the pyrimidine strand is the most critical for the specific interaction. Taking into account the recent findings about the regular hydration in the minor groove of the B-type dodecamer dCGCGAATTCGCG in solid-state, the different binding modes observed between the different polymers and antibiotics are explained by differences in their possibilities of hydration. Binding of netropsin to a double stranded deoxypolymer is interpreted as a local replacement of water molecules by netropsin in the minor groove hydration network which is typical of the B-form.

Chemical Phenomena↗
PubMed1982

Polynucleotide helix geometry and stability. Spectroscopic, antigenic and interferon-inducing properties of deoxyribose-, ribose-, or 2'-deoxy-2'-fluororibose-containing duplexes of poly(inosinic acid) . poly(cytidylic acid).

Circular dichroism, absorbance temperature profiles, antigenic properties, and interferon-inducing capacity of the nine double-stranded complexes between poly(inosinic acid) and poly(cytidylic acid) [(rI)n . (rC)n] and their deoxy- and 2'-deoxy-2'-fluoro-analogues were studied. The complexes containing only ribose or 2'-fluororibose chains showed similar CD spectra and thermal stabilities. Anti-(rI)n . (rC)n antibodies were well recognized by the duplexes containing 2'-fluororibose in either one strand. These two duplexes were also efficient interferon inducers. Presence of fluororibose in both strands decreased the affinity of anti-(rI)n . (rC)n antibodies slightly and abolished interferon-inducing activity. All polydeoxyriboside-containing complexes showed CD spectra significantly different from the previous group; they showed also 40- to 100-times lower affinity for the anti-(rI)n . (rC)n antibodies, and did not induce interferon. It is concluded that the structure of (rI)n . (rC)n, an A-type helix, is little perturbed by substitution of one or both strands by 2'-fluororibose. Substitution by deoxyribose in either strand considerably changes the structure of the helices. The hybrids containing poly(deoxycytidylic acid) retain at least some of the structural features of the B-type helix poly(deoxyinosinic acid) . poly(deoxycytidylic acid).

Animals↗
PubMed1982

Conformational transitions of poly(dA-dC).poly(dG-dT) induced by high salt or in ethanolic solution.

Poly(dA-dC).poly(dG-dT) was studied by circular dichroism in the presence of high CsCl concentrations and in ethanolic solutions. This alternating purine-pyrimidine duplex may undergo two conformational transitions from a B-type to a novel structure and subsequently into an A-form. Cs+ ions or increasing ethanol concentrations induced a change of the B-type CD spectrum and an inversion of the long wavelength CD band. Lowering the temperature below 0 C or addition of small amounts of Ca++ ions were particularly potent in producing a large negative CD band. A modified B-type structure or a conversion into a left-handed Z-form is considered for this conformational transition.

Circular Dichroism↗
PubMed1980

Magnetic circular dichroism study of the binding of netropsin and distamycin A with DNA.

The magnetic circular dichroism (MCD) of netropsin and distamycin-A is reported. New data for the interaction with dA ; dT base pairs in DNA were obtained from the MCD of their complexes with DNA duplex polymers. The MCD results allow an interpretation of the induced Cotton effects in the natural CD spectra of netropsin and distamycin-A complexes with DNA. While large distortions of the bases in DNA by the oligopeptide interaction is excluded, some subtle conformational variations of the DNA might explain the inhibition of the enzyme function of netropsin and distamycin-A on DNA.

Circular Dichroism↗
PubMed1979

Influence of nucleotide sequence on dA.dT-specific binding of Netropsin to double stranded DNA.

Using CD measurements the complex formation of Netropsin (Nt) with poly(dA-dC).poly(dT-dG) and its stability against high salt concentrations is compared with that of poly(dA).poly(dT) and poly(dA-dT).POLY(DT-dA). It is experimentally shown that the insertion of a dG.dC pair in dA.dT sequences strongly reduces the specific interaction of Nt with DNA duplexes. The specificity of the interaction is strongly increased by two or more consecutive thymine residues as present in thymine isostichs of double stranded DNA's.

Base Sequence↗
PubMed1978

Poly(dG).poly(dC) at neutral and alkaline pH: the formation of triple stranded poly(dG).poly(dG).poly(dC).

Alkaline titrations of different samples of poly(dG).poly(dC) and of the constituent homopolymers poly(dG) and poly(dC) have been performed in 0.15 M NaCl and their CD spectra followed. Sample I contained a slight excess of poly(dC) (52% C: 48% G) and showed a single reversible transition (pK = 11.9) due to the dissociation of double stranded poly(dG).poly(dC). Sample II, containing an excess of poly(dG) (43% C: 57% G), showed two transitions (pK1 = 11.4, PK2 = 11.9) the first one being only partially reversible. Examination of the CD spectra along the alkaline titrations indicated the presence of another hydrogen-bonded complex of higher G content. Mixing curves performed at pH 8 have confirmed the presence of a 2G: 1C complex, besides the double stranded complex. It can be formed in amounts up to 30% by mixing the two homopolymers, alkali treatment and heating. The CD spectra of the two complexes have been computed from the CD data of the mixing curves. This permitted the determination of the concentrations of both complexes and homopolymers in all samples. The ratio of triple to double stranded complex is not only dependent on the G/C ratio of the sample, but also a function of the previous physico-chemical conditions. These results explain the variability of many properties of different poly(dG).poly(dC) samples observed by other workers.

Centrifugation, Density Gradient↗
PubMed1978

Protonated polynucleotides structures - 22.CD study of the acid-base titration of poly(dG).poly(dC).

The acid-base titration (pH 8 --> pH 2.5 --> pH 8) of eleven mixing curve samples of the poly(dG) plus poly(dC) system has been performed in 0.15 M NaCl. Upon protonation, poly(dG).poly(dC) gives rise to an acid complex, in various amounts according to the origin of the sample. We have established that the hysteresis of the acid-base titration is due to the non-reversible formation of an acid complex, and the liberation of the homopolymers at the end of the acid titration and during the base titration: the homopolymer mixtures remain stable up to pH 7. A 1G:1C stoichiometry appears to be the most probable for the acid complex, a 1G:2C stoichiometry, as found in poly(C(+)).poly(I).poly(C) or poly(C(+)).poly(G).poly(C), cannot be rejected. In the course of this study, evidence has been found that the structural consequences of protonation could be similar for both double stranded poly(dG).poly(dC) and G-C rich DNA's: 1) protonation starts near pH 6, dissociation of the acid complex of poly(dG).poly(dC) and of protonated DNA take place at pH 3; 2) the CD spectrum computed for the acid polymer complex displays a positive peak at 255 nm as found in the acid spectra of DNA's; 3) double stranded poly(dG).poly(dC) embedded in triple-stranded poly(dG).poly(dG).poly(dC) should be in the A-form and appears to be prevented from the proton induced conformational change. The neutral triple stranded poly(dG).poly(dG).poly(dC) appears therefore responsible, although indirectly, for the complexity and variability of the acid titration of poly(dG).poly(dC) samples.

Circular Dichroism↗
PubMed1978

Protonated polynucleotides structures - 23. The acid-base hysteresis of poly(dG).poly(dC).

The large hysteresis observed during the acid-base titration of poly(dG). poly (dC) was studied by CD and potentiometric scanning curves. Intermediate scanning loops as well as the equilibrium and metastable branches of the hysteresis loop have been determined. The potentiometric titrations showed, however, that the various complexes were not discrete entities, but were linked in "polycomplexes" as had been already suggested. This prevented a thermodynamic study of the system. The acid-base titration was further investigated as a function of ionic strength and temperature. The pK's showed considerably lower ionic strength dependence than observed for polyribonucleotide complexes. The thermal transitions permitted to establish the relative stabilities of the various complexes between pH 2.5 and pH 12.0.

Circular Dichroism↗
PubMed1978

A simple method for the computation of first neighbour frequencies of DNAs from CD spectra.

A procedure for the computation of the first neighbour frequencies of DNA's is presented. This procedure is based on the first neighbour approximation of Gray and Tinoco. We show that the knowledge of all the ten elementary CD signals attached to the ten double stranded first neighbour configurations is not necessary. One can obtain the ten frequencies of an unknown DNA with the use of eight elementary CD signals corresponding to eight linearly independent polymer sequences. These signals can be extracted very simply from any eight or more CD spectra of double stranded DNA's of known frequencies. The ten frequencies of a DNA are obtained by least square fit of its CD spectrum with these elementary signals. One advantage of this procedure is that it does not necessitate linear programming, it can be used with CD data digitalized using a large number of wavelengths, thus permitting an accurate resolution of the CD spectra. Under favorable case, the ten frequencies of a DNA (not used as input data) can be determined with an average absolute error < 2%. We have also observed that certain satellite DNA's, those of Drosophila virilis and Callinectes sapidus have CD spectra compatible with those of DNA's of quasi random sequence; these satellite DNA's should adopt also the B-form in solution.

Animals↗