Structural Features of the (+)‐Yatakemycin/d(GACTAATTGAC)‐(GTCAATTAGTC) Complex – Quantum Mechanical Calculation of NMR Parameters as a Tool for the Characterization of Ligand/DNA Interactions

Abstract

Keywords:Minor groove binders / NMR spectroscopy / Calculation of NMR parameters (+)-Yatakemycin is a new and potent member of a class of natural antitumor compounds that derive their biological activities from specific alkylation of adenine residues in the minor grooves of AT-rich tracts. We have analyzed the covalent complex formed between (+)-yatakemycin and the d(GACTAATTGAC)-(GTCAATTAGTC) duplex, and have established that the ligand covalently binds to the A5 residue. For this purpose we used a hybrid approach based on 2D-

Quantum Mechanical Calculation of NMR Parameters in the Stereostructural Determination of Natural Products

“…Recently, we applied QM calculation of 1 H NMR chemical shifts for the analysis of the covalent complex formed between (+)-yatakemycin and the d(GACTAATTGAC)-(GTCAATTAGTC) duplex (section 5), showing that the calculated NMR parameters can be a useful tool for the structural characterization of ligand-macromolecule interactions. [24] 2. Quantum Mechanical Calculation of NMR Chemical Shifts 2.1 QM Calculation of 13 C NMR Chemical Shifts for the Stereochemical Assignment of Bonannione B Analysis of the relative configuration of the flavonoid bonannione B (1, Scheme 1), isolated from the plant Bonannia graeca, is reported [25] as a straightforward application of 13 C NMR chemical shift calculation.…”

“…Recently, we applied QM calculation of 1 H NMR chemical shifts for the analysis of the covalent complex formed between (+)-yatakemycin and the d(GACTAATTGAC)-(GTCAATTAGTC) duplex (section 5), showing that the calculated NMR parameters can be a useful tool for the structural characterization of ligand-macromolecule interactions. [24]…”

DFT/NMR integrated approach: a valid support to the total synthesis of chiral molecules

“…This process, in fact, is essential in several fields that not only include the total synthesis of the molecules under investigation but also the understanding, at the molecular level, of the biological mechanism of active natural compounds; stereochemical knowledge is also fundamental for structure-activity studies of drug-receptor systems. [1] Basically, there are different approaches to identify the exact structure and/or stereochemistry of organic products. The classic chemical approach, represented by the total synthesis, has played a major role in the structural assignments and revision for a long time, but the additional costs in terms of time and money represent some of its most important weaknesses.…”

Nucleotides and Nucleic Acids; Oligo- and Polynucleotides

“…809 Other antitumor agents bound to duplex DNA that have been solved by NMR include Topotecan 810 and Yatakemycin. 811 Several G-quadruplex structures have been examined by NMR, mostly investigating the effects of different monovalent ions stabilising the quadruplex structure. To try to identify where sodium ions and water are precisely in G-quadruplexes NMR spectra have been recorded using 2 H 2 17 O and 23 Na, 812 whilst 87 Rb has been used to demonstrate the stabilisation of G-quadruplexes by rubidium ions.…”