Ion triggered alkylation of biological targets by silyloxy aromatic agents

US5296350A · kind A · utility

Assignee

• The Research Foundation of the State University of New York · US

Inventors

• Steven E. Rokita · Port Jefferson, US
• Tianhu Li · San Diego, US

Key dates

• Filing date: Oct 31, 1990
• Grant date: Mar 22, 1994
• Expiry date: Oct 31, 2010

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07H23/00
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A sequence directed reagent is constructed by conjugating a methyl silyloxy aromatic derivative to a hexamethylamino linker attached to either the 5' or 3' terminus of an oligonucleotide. Annealing this modified fragment of DNA to its complementary sequence allows for target modification subsequent to ionic activation. The product of this reaction is a covalent crosslink between the reagent and target strands resulting from an alkylation of DNA by the activated silyloxy aromatic derivative. In a preferred embodiment, a nitrophenyl group is attached to the methyl group of the silyloxy aromatic derivative. This reagent is similarly linked to an oligonucleotide probe. Activation of this probe linked alkylating agent by an ionic signal, (X) which may naturally occur, or may be introduced into the media containing the target molecule, such as by the introduction of a salt (MX).