Self-immolative probes for enzyme activity detection

摘要

Provided is a compound comprising the structure:
(SIG)-(SI-MOD)m.;In this compound, SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. With this compound, when MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided is a method of determining whether a sample comprises an activator, using the above-described compound. Additionally provided is a method of determining whether a cell comprises a nitroreductase using the above-described compound where nitroreductase is the activator. Further provided is a method of determining whether a mammalian cell is hypoxic using the above-described compound where nitroreductase is the activator. A method of detecting a microorganism that comprises a nitroreductase, using the above-described compound where nitroreductase is the activator, is also provided. Also provided is a method of identifying nitroreductase in a sample, using the above-described compound where nitroreductase is the activator.

主权项

1. A composition, comprising:
a compound represented by the structure: wherein SIG is a signaling moiety, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG when cleaved from SI, wherein each AA is independently an amino acid of an amino acid sequence, PTM is a prost-translational modification bound to the side chain of any of the amino acids of the amino acid sequence, n is an integer representing the total number of amino acids in the sequence, wherein n is from 1 to about 200, and m is an integer from 1 to about 10, and where when the PTM is removed from the compound by an enzyme capable thereof, a protease or peptidase is then able to remove the amino acid sequence, allowing self-cleavage of SI and SIG; and the protease or peptidase that is able to remove the amino acid sequence when PTM is removed by the enzyme.