Universal linker compositions for the release or transfer of chemical agents from a polynucleotide

US7745614B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Eric T. Kool · Stanford, US
• Hiroshi Abe · Saitama, JP

Key dates

• Filing date: Sep 1, 2005
• Grant date: Jun 29, 2010
• Expiry date: Feb 25, 2028

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S977/792
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A universal linker structure is provided, in which a functional group and activating leaving group are placed on a tether, allowing the placement of an electrophile at the end of any nucleic acid sequence. The electrophile on the tether can react with a second nucleic acid carrying a nucleophile when the two nucleic acids are hybridized near one another, resulting in release of the leaving group, and creation of a functional change. The linker can be designed to destabilize the ligation product without slowing the rate of reaction. This lowers product inhibition, and the target DNA or RNA can become a catalyst for isothermally generating multiple signals for detection. This enhanced signal is demonstrated in solution experiments and in solid supported assays. The universal linkers of the present invention are simple and inexpensive to prepare, and can be appended to any polynucleotide in automated steps on a standard DNA synthesizer.