Differential hydration of homopurine sequences relative to alternating purine/pyrimidine sequences.
The minor groove ligand distamycin A has been used to probe the relative hydration of the minor groove of eight synthetic polynucleotides of known sequence and composition. A combination of densimetric, calorimetric, and temperature-dependent spectroscopic techniques have been used to obtain complete thermodynamic profiles (delta Gzero, delta Hzero, delta Szero, and delta Vzero) for the association of distamycin A to all polymer duplexes. In 10 mM phosphate buffer, pH 7, binding of the drug to each of the polymeric duplexes resulted in characteristic negative changes in both the volume and enthalpy. Although the binding constants were found to be identical for pairs of isomer polynucleotides having identical compositions but different sequences, the values of delta Hzero, delta Szero, and delta Vzero of each such pair were remarkably different. The entropy changes were found to roughly parallel the volume changes; no such trend was seen between delta Hzero and delta Vzero. The data support the hypothesis that the volume changes observed for these systems reflect the coulombic-hydration contribution to the entropy. The heteropolymer duplexes generated much larger exothermic contributions, less favorable entropies and larger volume contractions than did the corresponding homopolymer duplexes of identical composition, and strongly suggest that polynucleotides with homopurine sequences are more hydrated than polynucleotides with alternating purine/pyrimidine sequences. In addition, it was found that duplexes containing guanine sharply reduced the affinity for the drug, also lowering the exothermicity but raising the entropy. This may be explained by the presence of an amino group in the minor groove that prevents hydrogen bonding. Substitution of the guanine with inosine reversed this trend in the thermodynamic properties. Furthermore, substitution of poly(dA) for poly(rA) in a duplex produced a similar reduction in the affinity, while raising the exothermic contribution and greatly reducing the favorable entropy effect in agreement with an apparent increase in the hydration state.
Rentzeperis
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Department of Chemistry, New York University, New York 10003.
Kupke
D W
DW
Marky
L A
LA
D001483:Base Sequence; D002151:Calorimetry; D004214:Distamycins / Q000378:metabolism; D009429:Netropsin / Q000378:metabolism; D011119:Polynucleotides / Q000737:chemistry; D011687:Purines / Q000737:chemistry* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D004214:Distamycins; D011119:Polynucleotides; D011687:Purines; D011743:Pyrimidines; D014867:Water; D009429:Netropsin; C030000:stallimycin