Netropsin-poly(dA-dT) complex in solution: structure and dynamics of antibiotic-free base pair regions and those centered on bound netropsin.
The biphasic duplex-to-strand transition for the netropsin.poly(dA-dT) complex, phosphate/drug mole ratio (P/D) = 50, has been investigated by high-resolution proton nuclear magnetic resonance (NMR) spectroscopy at the nonexchangeable base and sugar protons in 0.1 M cacodylate solution. The NMR spectral parameters monitor the structure and dynamics of the opening of antibiotic-free base pair regions (55 degrees-65 degrees) and the opening of base regions centered on bound netropsin (90 degrees-100 degrees). The gradual addition of netropsin to poly(dA-dT) results in structural perturbations extending into the antibiotic-free base pair regions that begin to level off above 0.02 antibiotic molecules per polynucleotide phosphate (P/D = 50). The NMR chemical shift parameters at the antibiotic-free base pair regions in the P/D = 50 complex suggest changes in the glycosidic torsion angles of the deoxyadenosine and thymidine residues and less pronounced changes in the base pair overlap geometries. The dissociation rates of the antibiotic-free base pair regions are at least an order of magnitude slower in the P/D = 50 netropsin.poly(dA-dT) complex compared to related parameters for poly(dA-dT) and the P/D = 50 ethidium bromide-poly(dA-dT) complex. There is decreased segmental mobility at the antibiotic-free strand regions in the temperature range (65 degrees-90 degrees) between the two transitions in the biphasic melting curve of the P/D = 50 netropsin-poly(dA-dT) complex. Netropsin stabilizes at least five base pairs, with their center at its binding site.
D006146:Guanidines; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009429:Netropsin; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D011067:Poly dA-dT; D011089:Polydeoxyribonucleotides; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D006146:Guanidines; D011089:Polydeoxyribonucleotides; D011067:Poly dA-dT; D009429:Netropsin
J Mol Biol. 1965 Feb;11:213-22
14290341
Biopolymers. 1977 Apr;16(4):857-73
851584
J Theor Biol. 1977 Mar 7;65(1):189-201
850419
J Theor Biol. 1977 Mar 7;65(1):171-88
850418
Proc Natl Acad Sci U S A. 1976 Mar;73(3):674-8
1062778
J Biol Chem. 1974 Nov 10;249(21):6719-31
4371420
Prog Nucleic Acid Res Mol Biol. 1975;15(0):285-318
1094496
J Biol Chem. 1975 Apr 10;250(7):2698-702
164447
Eur J Biochem. 1971 Jul 29;21(2):269-78
4935203
Nucleic Acids Res. 1976 Jun;3(6):1521-32
958896
Biopolymers. 1976 Jul;15(7):1345-75
949539
J Mol Biol. 1971 May 28;58(1):329-48
5088933
Nucleic Acids Res. 1974 Mar;1(3):503-30
10793682