Process for labeling nucleic acids using psoralen derivatives

Abstract

A labeling reagent of the formula: [A][B]L is prepared where A is an alkylating intercalation moiety, B is a divalent organic spacer arm moiety with a straight chain of at least two carbon atoms, and L is a monovalent label moiety capable of producing a detectable signal, e.g., a signal detectable by spectroscopic, photochemical, chemical, immunochemical or biochemical means. Preferably A is a 4'-methylene-substituted psoralen moiety, and most preferably A is a 4'-methylene-substituted 4,5',8-trimethylpsoralen moiety. This reagent may be used to label nucleic acids, preferably DNA, by intercalating the alkylating intercalation moiety of the reagent into an at least partially double-stranded nucleic acid to form a complex and activating the complex to cause covalent bonding between the reagent and the nucleic acid. Preferably, the labeled nucleic acid is a hybridization probe for detecting nucleic acid sequences capable of hybridizing with a hydridizing region of the nucleic acid. Also preferably the label moiety is non-radioactive. This reagent may also be used in chromosome banding to label specific regions of chromosomes and thereby differentiate them.

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