Hydrolysis-Resistant Ester-Based Linkers for Development of Activity-Based NIR Bioluminescence Probes.

ABSTRACT: Activity-based sensing (ABS) probes equipped with a NIR bioluminescence readout are promising chemical tools to study cancer biomarkers owing to their high sensitivity and deep tissue compatibility. Despite the demand, there is a dearth of such probes because NIR substrates (e.g., BL660 (a NIR luciferin analog)) are not equipped with an appropriate attachment site for ABS trigger installation. For instance, our attempts to mask the carboxylic acid moiety with standard self-immolative benzyl linkers resulted in significant background signals owing to undesirable ester hydrolysis. In this study, we overcame this longstanding challenge by rationally designing a new hydrolysis-resistant ester-based linker featuring an isopropyl shielding arm. Compared to the parent, the new design is 140.5-fol

SUBMITTER: Yadav AK 

PROVIDER: S-EPMC10120059 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature