Sequence specific molecular recognition by a monocationic lexitropsin of the decadeoxyribonucleotide d-[CATGGCCATG]2: structural and dynamic aspects deduced from high field 1H-NMR studies.
All 1H-NMR resonances of d-[CATGGCCATG]2 and the 1:1 complex of lexitropsin 1 and the DNA were assigned by the NOE difference, COSY and NOESY methods. Addition of 1 causes the base and imino protons for the sequence 5'-CCAT to undergo the most marked drug-induced chemical shift changes, thereby indicating that 1 is located in this base pair sequence. NOEs confirmed the location and orientation of the drug in the 1:1 complex, with the amino terminus oriented to C(6). The van der Waals interaction between H12a,b of 1 and AH2(8) may be responsible for reading of the 3' A.T base pair in the 5'-CCAT sequence. Exchange NMR effects allow an estimate of approximately equal to 62 s-1 for the intramolecular "slide-swing" exchange of the lexitropsin between two equivalent binding sites with delta G = 58 +/- 5 kJ mol-1 at 301 degrees K.
Lee
M
M
Department of Chemistry, University of Alberta, Edmonton, Canada.
Hartley
J A
JA
Pon
R T
RT
Krowicki
K
K
Lown
J W
JW
D003198:Computer Simulation; D004268:DNA-Binding Proteins; D006146:Guanidines; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009038:Motion; D009429:Netropsin / Q000031:analogs & derivatives; D009838:Oligodeoxyribonucleotides; D011485:Protein Binding
D004268:DNA-Binding Proteins; D006146:Guanidines; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; C053654:lexitropsin; D009429:Netropsin