California Institute of Technology

Columbia University

Jacqueline K Barton

Michael G Hill

Shana O Kelley

Brian P Hudson

Brian A Jackson

Alyson Weidmann

Alexis Christine Komor

Henrik Junicke

Curtis J Schneider

Elizabeth M Boon

Russell Ernst

Brian Zeglis

Natalie B Muren

Irvin H Lau

Jonathan Hart

Mi Hee Lim

Ariel L Furst

A two-electrode detection system having target substrates including nucleic acids, proteins, and/or small molecules on specifically defined regions of a single surface. The spatial distribution of the target substrate on the surface allows for more accurate substrate interactions and analysis. Additionally, the detection system of the present invention allows for patterning of different target substrates, thereby affording more accurate analysis of multiple substrate targets.

Electrochemical substrate patterning and analyte detection on a two-electrode platform

A composition including a metalloinsertor conjugate that specifically targets mismatch repair (MMR)-deficient cells includes a complex represented by Formula I.M(L)(L)(L)(L)(L)&#x2003;&#x2003;Formula I Selective cytotoxicity may be induced in MMR-deficient cells upon uptake of the metalloinsertor conjugate. Metalloinsertor complexes conjugated with platinum (Pt) may allow for more specific targeting of platinum anticancer agents.

Metalloinsertor conjugates

A composition including a Rh or Ru metalloinsertor complex specifically targets mismatch repair (MMR)-deficient cells. Selective cytotoxicity is induced in MMR-deficient cells upon uptake of the inventive metalloinsertor complexes.

Metalloinsertor complexes targeted to DNA mismatches

In accordance with the present invention there are provided sterically demanding intercalators. These compounds are useful for detection of a base-pair mismatch, such as by measuring fluorescence of complexes formed by the compounds of the invention and nucleic acid duplexes. The compounds are also capable of catalyzing photolytic cleavage of nucleic acids.

Compounds and methods for nucleic acid mismatch detection

In accordance with the present invention there is provided a new class of sterically demanding metallo-intercalators. These compounds intercalate between bases in a duplex polynucleotide, but only where the bases are not fully complementary, for example, where there is a base-pair mismatch. The compounds are sufficiently sterically demanding that intercalation between bases in fully complementary duplexes does not occur to a significant degree. These mismatch intercalators are useful for detecting DNA and RNA defects, for diagnosing disorders characterized by the presence or increase in DNA and/or RNA defects, and for treating such disorders. Further, the compounds are capable of catalyzing photolytic cleavage of nucleic acids at relatively long wavelengths, and under normal sunlight.

Methods and compositions for detecting polynucleotide duplex damage and errors

Compositions and methods for electrochemical detection and localization of genetic point mutations, common DNA lesions and other base-stacking perturbations within oligonucleotide duplexes adsorbed onto electrodes and their use in biosensing technologies are described. An intercalative, redox-active moiety (such as an intercalator or nucleic acid-binding protein) is adhered and/or crosslinked to immobilized DNA duplexes at different separations from an electrode and probed electrochemically in the presence or absence of a non-intercalative, redox-active moiety. Interruptions in DNA-mediated electron-transfer caused by base-stacking perturbations, such as mutations or binding of a protein to its recognition site are reflected in a difference in electrical current, charge and/or potential.

Electrochemical sensor using intercalative, redox-active moieties

Detection and treatment of duplex polynucleotide damage

Compositions and methods for electrochemical detection and localization of genetic point mutations and other base-stacking perturbations within oligonucleotide duplexes adsorbed onto electrodes and their use in biosensing technologies are described. An intercalative, redox-active moiety (such as an intercalator or nucleic acid-binding protein) is adhered and/or crosslinked to immobilized DNA duplexes at different separations from an electrode and probed electrochemically in the presence or absence of a non-intercalative, redox-active moiety. Interruptions in DNA-mediated electron-transfer caused by base-stacking perturbations, such as mutations or binding of a protein to its recognition site are reflected in a difference in electrical current, charge and/or potential.

Duplex polynucleotides containing damage or errors are detected with hindered intercalating compounds which are capable of intercalating only in the presence of such damage or error. Conditions characterized by the presence of polynucleotide errors or damage are treated with such compounds that are capable of catalyzing polynucleotide cleavage with light. Suitable compound include compounds of the formula:

Growing community of inventors

San Marino, CA, United States of America

Jacqueline K Barton