The integral divalent cation within the intermolecular purine*purine. pyrimidine structure: a variable determinant of the potential for and characteristics of the triple helical association.
In vitro assembly of an intermolecular purine*purine.pyrimidine triple helix requires the presence of a divalent cation. The relationships between cation coordination and triplex assembly were investigated, and we have obtained new evidence for at least three functionally distinct potential modes of divalent cation coordination. (i) The positive influence of the divalent cation on the affinity of the third strand for its specific target correlates with affinity of the cation for coordination to phosphate. (ii) Once assembled, the integrity of the triple helical structure remains dependent upon its divalent cation component. A mode of heterocyclic coordination/chelation is favorable to triplex formation by decreasing the relative tendency for efflux of integral cations from within the triple helical structure. (iii) There is also a detrimental mode of base coordination through which a divalent cation may actively antagonize triplex assembly, even in the presence of other supportive divalent cations. These results demonstrate the considerable impact of the cationic component, and suggest ways in which the triple helical association might be positively or negatively modulated.
Blume
S W
SW
Comprehensive Cancer Center and Department of Medicine and Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Lebowitz
J
J
Zacharias
W
W
Guarcello
V
V
Mayfield
C A
CA
Ebbinghaus
S W
SW
Bates
P
P
Jones
D E
DE
Trent
J
J
Vigneswaran
N
N
Miller
D M
DM
D020029:Base Pairing; D002413:Cations, Divalent / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry*; D016373:DNA, Antisense; D006801:Humans; D008274:Magnesium; D019216:Metals, Heavy; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011685:Purine Nucleotides / Q000737:chemistry; D011742:Pyrimidine Nucleotides / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D002413:Cations, Divalent; D016373:DNA, Antisense; D019216:Metals, Heavy; D009838:Oligodeoxyribonucleotides; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; C051802:triplex DNA; D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase; D008274:Magnesium