Sequence specific molecular recognition by a monocationic lexitropsin of the decadeoxyribo-nucleotide d-[CATGGCCATGl2: structural and dynamic aspects deduced from high Held1H-NMR studies

Abstract
All 1H-NMR resonances of d-[CATGGCCATG]2 and the 1:1 complex of lexitropsin 1 and the DNA were assigned by the HOE difference, COSY and NOESY aethods. 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 AB2(8) nay be responsible for reading of the 3' A.T base pair in the 5'-CCAT sequence. Exchange NMR effects allow an estimate of ≃ 62 s−1 for the intramolecular “slide-swing” exchange of the lexitropsin between two equivalent binding sites with δG≠ = 58 ± 5 kJ mol−1 at 301°K.