Ion triggered alkylation of biological targets by silyloxy aromatic agents

US5493012A · 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
• Qingping Zeng · Thousand Oaks, US

Key dates

• Filing date: Jun 2, 1993
• Grant date: Feb 20, 1996
• Expiry date: Jun 2, 2013

Classification

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

Abstract

A silyloxy aromatic derivative capable of alkylating a target biological molecule when activated by ionic strength. A sequence directed reagent may be constructed by conjugating a methyl silyloxy aromatic derivative to a hexamethyiamino 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 or bromo group is attached to a methyl group of the silyloxy aromatic derivative. This reagent may be similarly linked to an oligonucleotide probe. Activation of the 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).