Homoallylamines As Formaldehyde-Responsive Triggers With Imaging Applications

The invention concerns the use of homoallylamines which undergo a 2-aza-Cope reaction upon condensation with formaldehyde (FA) which can be coupled to a ftuorogenic, colorimetric, or biolurninescent response. Traditional methods for biological FA detection rely on sample destruction and/or extensive processing, resulting in a loss of spatiotemporal information. The invention, as showcased by the tw'! chemical probes FAP-1 and FP-1, enables detection of biological FA with high selectivity in aqueous buffer and in living samples in a non-invasive manner. The hornoallylamine trigger can be generalized to cage a large variety of different fluorophores, chromophores, and bioluminescent molecules (e.g. tuciferin). 

Measuring FA in aqueous buffer (e.g. as a proxy for demethylase enzyme activity, potentially in a high-throughput screen format), for fluorescent imaging of FA in cell culture, and for bioluminescent imaging of FA in live animals.