Binding kinetics of bisintercalator Triostin a with optical tweezers force mechanics.

The binding kinetics of the intercalative binding of Triostin A to lambda-DNA was investigated by measuring the force extension response of the DNA-ligand complexes with an optical tweezers system. These force response curves, containing the information about different binding properties, were analyzed based on a recent method (put forth by another research group) for monointercalators that was extended to bisintercalators. Our binding analysis reveals an exponential dependence of the association constant on the applied external force as well as a decreasing binding site size. In general, our results are in agreement with those for the monointercalator ethidium. However, to explain the high-force binding site size, a new model for bisintercalation of Triostin A at high forces is proposed.

[1]  Micah J. McCauley,et al.  Mapping the phase diagram of single DNA molecule force-induced melting in the presence of ethidium. , 2005, Physical review letters.

[2]  M. Waring,et al.  Bifunctional intercalation and sequence specificity in the binding of quinomycin and triostin antibiotics to deoxyribonucleic acid. , 1978, The Biochemical journal.

[3]  Ioulia Rouzina,et al.  Thermodynamics of DNA interactions from single molecule stretching experiments. , 2002, Accounts of chemical research.

[4]  Andy Sischka,et al.  Compact microscope-based optical tweezers system for molecular manipulation , 2003 .

[5]  Nancy R Forde,et al.  Mechanical processes in biochemistry. , 2004, Annual review of biochemistry.

[6]  D. Crothers Calculation of binding isotherms for heterogeneous polymers , 1968, Biopolymers.

[7]  M. Hegner,et al.  DNA Mechanics Affected by Small DNA Interacting Ligands , 2002 .

[8]  P. V. von Hippel,et al.  Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. , 1974, Journal of molecular biology.

[9]  D. Anselmetti,et al.  Molecular mechanisms and kinetics between DNA and DNA binding ligands. , 2005, Biophysical journal.

[10]  C. Bustamante,et al.  Overstretching B-DNA: The Elastic Response of Individual Double-Stranded and Single-Stranded DNA Molecules , 1996, Science.

[11]  M. Waring,et al.  Preparation and DNA-binding properties of substituted triostin antibiotics , 1983, Antimicrobial Agents and Chemotherapy.

[12]  A. Rich,et al.  The molecular structure of a DNA-triostin A complex. , 1984, Science.

[13]  B G de Grooth,et al.  Single-molecule manipulation of double-stranded DNA using optical tweezers: interaction studies of DNA with RecA and YOYO-1. , 1999, Cytometry.

[14]  Micah J. McCauley,et al.  Quantifying force-dependent and zero-force DNA intercalation by single-molecule stretching , 2007, Nature Methods.

[15]  F. John,et al.  Stretching DNA , 2022 .