Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements.

Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements. Research Abstract Details 

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Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements. Abstract Text:

Lauren K Wolf,Yang Gao,Rosina M Georgiadis,

We demonstrate the use of surface plasmon resonance (SPR) imaging for direct detection of small-molecule binding to surface-bound DNA probes. Using a carefully designed array surface, we quantitatively discriminate between the interactions of a model drug with different immobilized DNA binding sites. Specifically, we measure the association and dissociation intercalation rates of actinomycin-D (ACTD) to and from double-stranded 5'-TGCT-3' and 5'-GGCA-3' binding sites. The rates measured provide mechanistic information about the DNA-ACTD interaction; ACTD initially binds nonspecifically to DNA but exerts its activity by dissociating slowly from strong affinity sites. We observe a slow dissociation time of kd-1 = 3300 +/- 100 s for ACTD bound to the strong affinity site 5'-TGCT-3' and a much faster dissociation time (210 +/- 15 s) for ACTD bound weakly to the site 5'-GGCA-3'. These dissociation rates, which differ by an order of magnitude, determine the binding affinity for each site (8.8 x 10(6) and 1.0 x 10(6) M(-1), respectively). We assess the effect the surface environment has on these biosensor measurements by determining kinetic and thermodynamic constants for the same DNA-ACTD interactions in solution. The surface suppresses binding affinities approximately 4-fold for both binding sites. This suppression suggests a barrier to DNA-drug association; ACTD binding to duplex DNA is approximately 100 times slower on the surface than in solution.

Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements. Publishing Authors By Initials

LK Wolf,Y Gao,RM Georgiadis,

For similar investigative techniques: chemistry, analytical: titrimetry research abstracts see: investigative techniques: chemistry, analytical: titrimetry research

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Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 129

Page Numbers: 10503-11

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 8

MONTH: 08

YEAR: 2007

Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements. Keywords Mesh Terms:

KEYWORDS: Titrimetry

MESH TERMS: chemistry

Chemical & Substance for Abstract: Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for Kinetic discrimination of sequence-specific DNA-drug binding measured by surface plasmon resonance imaging and comparison to solution-phase measurements.

AFFILIATION: Department of Chemistry, Metcalf Center for Science and Engineering, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA89562

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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