DNA Binding mode and sequence specificity of piperazinylcarbonyloxyethyl derivatives of anthracene and pyrene
Artikel i vetenskaplig tidskrift, 1999

Four novel piperazinylcarbonyloxyethyl derivatives of anthracene and pyrene have been prepared and investigated with respect to sequence specificity and synergism between hydrophobic and electrostatic effects upon binding to DNA. Linear and circular dichroism spectroscopy was used to assess the orientation of the aromatic chromophores relative to the nucleobases. Anthracene and pyrene derivatives 2a and 3 are both concluded to bind to homo-polynucleotide poly(dA-dT)(2) by intercalation of their aromatic moieties between base pairs, with a binding constant K-AT of 4 x 10(5) M-1 and 2 x 10(6) M-1, respectively. Significantly reduced affinities (K-GC = 3 x 10(4) M-1 and 10(5) M-1, respectively) are observed with poly(dG-dC)(2), due to less favorable interactions of the piperazinium tail in the minor groove. Base pair specificity is reflected in the binding thermodynamics, with the binding to AT being more enthalpically driven than the binding to GC. Phenyl substitution at the quaternary piperazinium site of the anthracene derivative 2b, does not affect the ratio K-AT/K-GC, but reduces the affinity for both AT End GC slightly. Moreover, the phenyl group in the 10-position of 4 prevents intercalation, and apparently, this compound binds externally to both AT and GC duplex polynucleotides. The results are discussed in terms of general features of the interactions of the intercalating and minor-groove binding molecular moieties, and their interplay with each other, with potentials for tuning specificity.

Författare

Hans-Christian Becker

Institutionen för fysikalisk kemi

Bengt Nordén

Institutionen för fysikalisk kemi

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 121 51 11947-11952

Styrkeområden

Nanovetenskap och nanoteknik

Energi

Livsvetenskaper och teknik

Materialvetenskap

Ämneskategorier

Fysikalisk kemi

Fundament

Grundläggande vetenskaper

DOI

10.1021/ja991844p

Mer information

Skapat

2017-10-07