Stabilization of Double Stranded Homologous Poly(dA)·Poly(dT) by Taxol.
Identifieur interne : 003656 ( Main/Merge ); précédent : 003655; suivant : 003657Stabilization of Double Stranded Homologous Poly(dA)·Poly(dT) by Taxol.
Auteurs : G. Bischoff [Allemagne] ; U. Gromann ; S. Lindau ; E. Birch-Hirschfeld ; R. Bischoff ; C. Bohley ; W V Meister ; S. HoffmannSource :
- Journal of biomolecular structure & dynamics [ 1538-0254 ] ; 2000.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : Polydeoxyribonucleotides.
- chemical : Paclitaxel, Poly dA-dT, Polynucleotides.
- Animals, Circular Dichroism, Nucleic Acid Conformation.
Abstract
Abstract The nucleic acid activity of taxol and paclitaxel was investigated with synthetic and natural oligo- and polynucleotides. The polynucleotides poly(dA)·poly(dT), poly(dG)·poly(dC), poly [d(A-T)]·poly[d(A-T)], poly[d(G-C)]·poly[d(G-C)] and calf thymus DNA were used. The oligonucleotides are 24-mers with d(purine)(24)·d(pyrimidine)(24) strands, as well as d[(purine)(x)-(pyrimidine)(x)]·d[(purine)(x)-(pyrimidine)(x)] sequences. The study was performed with spectroscopic and calorimetric methods in dilute and condensed DNA-solutions. In a recent study, taxol and paclitaxel showed molecular recognition of AT nucleotides with a high affinity to homologous (dA)·(dT) sequences; no interaction with GC nucleotides could be observed. An astonishing stabilization of the DNA duplex up to ΔT(m) = 25°C was measured by thermal denaturation with poly(dA)·poly(dT)/paclitaxel complexes. Circular dichroism signals of DNA (24-mer) containing homologous (dA)·(dT) tracts increased with increasing amount of the drug; for the other oligo- and polynucleotides no change in the spectra could be found. Contrary to this findings, circular dichroism (CD) spectra of poly(dA)·poly(dT)/paclitaxel complexes displayed reduced intensities of the signals at increasing drug concentrations. These findings in dilute solutions were complemented by differential scanning calorimetric investigations in condensed states (only calf thymus DNA tested). Increasing enthalpies by increasing amount of the drug point to a stabilization. Simple phosphate backbone interaction in the narrow groove of (dA)·(dT) tracts could be a sufficient explanation for all the results. Hydrophilic side groups of the drug interact with the phosphate and clip the strands together, while the hydrophobic parts of the molecule may disturb the polynucleobase formation.
DOI: 10.1080/07391102.2000.10506640
PubMed: 22607443
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Bischoff</name><affiliation wicri:level="1"><nlm:affiliation>a Martin Luther University Halle-Wittenberg, Institute of Biochemistry , Kurt-Mothes-Str. 3 , D-06120 , Halle (Saale) , Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>a Martin Luther University Halle-Wittenberg, Institute of Biochemistry , Kurt-Mothes-Str. 3 , D-06120 , Halle (Saale) </wicri:regionArea><wicri:noRegion>Halle (Saale) </wicri:noRegion><wicri:noRegion>Halle (Saale) </wicri:noRegion><wicri:noRegion>Halle (Saale) </wicri:noRegion></affiliation></author><author><name sortKey="Gromann, U" sort="Gromann, U" uniqKey="Gromann U" first="U" last="Gromann">U. Gromann</name></author><author><name sortKey="Lindau, S" sort="Lindau, S" uniqKey="Lindau S" first="S" last="Lindau">S. Lindau</name></author><author><name sortKey="Birch Hirschfeld, E" sort="Birch Hirschfeld, E" uniqKey="Birch Hirschfeld E" first="E" last="Birch-Hirschfeld">E. Birch-Hirschfeld</name></author><author><name sortKey="Bischoff, R" sort="Bischoff, R" uniqKey="Bischoff R" first="R" last="Bischoff">R. Bischoff</name></author><author><name sortKey="Bohley, C" sort="Bohley, C" uniqKey="Bohley C" first="C" last="Bohley">C. Bohley</name></author><author><name sortKey="Meister, W V" sort="Meister, W V" uniqKey="Meister W" first="W V" last="Meister">W V Meister</name></author><author><name sortKey="Hoffmann, S" sort="Hoffmann, S" uniqKey="Hoffmann S" first="S" last="Hoffmann">S. Hoffmann</name></author></analytic><series><title level="j">Journal of biomolecular structure & dynamics</title><idno type="eISSN">1538-0254</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Circular Dichroism</term><term>Nucleic Acid Conformation</term><term>Paclitaxel</term><term>Poly dA-dT</term><term>Polydeoxyribonucleotides (chemistry)</term><term>Polynucleotides</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Conformation d'acide nucléique</term><term>Dichroïsme circulaire</term><term>Paclitaxel</term><term>Poly DA-DT</term><term>Polydésoxyribonucléotides ()</term><term>Polynucléotides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Polydeoxyribonucleotides</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Paclitaxel</term><term>Poly dA-dT</term><term>Polynucleotides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Circular Dichroism</term><term>Nucleic Acid Conformation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Conformation d'acide nucléique</term><term>Dichroïsme circulaire</term><term>Paclitaxel</term><term>Poly DA-DT</term><term>Polydésoxyribonucléotides</term><term>Polynucléotides</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract The nucleic acid activity of taxol and paclitaxel was investigated with synthetic and natural oligo- and polynucleotides. The polynucleotides poly(dA)·poly(dT), poly(dG)·poly(dC), poly [d(A-T)]·poly[d(A-T)], poly[d(G-C)]·poly[d(G-C)] and calf thymus DNA were used. The oligonucleotides are 24-mers with d(purine)(24)·d(pyrimidine)(24) strands, as well as d[(purine)(x)-(pyrimidine)(x)]·d[(purine)(x)-(pyrimidine)(x)] sequences. The study was performed with spectroscopic and calorimetric methods in dilute and condensed DNA-solutions. In a recent study, taxol and paclitaxel showed molecular recognition of AT nucleotides with a high affinity to homologous (dA)·(dT) sequences; no interaction with GC nucleotides could be observed. An astonishing stabilization of the DNA duplex up to ΔT(m) = 25°C was measured by thermal denaturation with poly(dA)·poly(dT)/paclitaxel complexes. Circular dichroism signals of DNA (24-mer) containing homologous (dA)·(dT) tracts increased with increasing amount of the drug; for the other oligo- and polynucleotides no change in the spectra could be found. Contrary to this findings, circular dichroism (CD) spectra of poly(dA)·poly(dT)/paclitaxel complexes displayed reduced intensities of the signals at increasing drug concentrations. These findings in dilute solutions were complemented by differential scanning calorimetric investigations in condensed states (only calf thymus DNA tested). Increasing enthalpies by increasing amount of the drug point to a stabilization. Simple phosphate backbone interaction in the narrow groove of (dA)·(dT) tracts could be a sufficient explanation for all the results. Hydrophilic side groups of the drug interact with the phosphate and clip the strands together, while the hydrophobic parts of the molecule may disturb the polynucleobase formation.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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