Rational Design of Pyrido[3,2-b]indolizine as a Tunable Fluorescent Scaffold for Fluorogenic Bioimaging

Abstract

Novel fluorescent scaffolds are highly demanding for a wide range of applications in biomedical investigation. To meet this demand, the pyrido[3,2-b]indolizine scaffold was designed as a versatile organic fluorophore. With the aid of computational modeling, fluorophores offering tunable emission colors (blue to red) were constructed. Notably, constructed fluorophores absorb lights in the visible range (>400 nm) despite their small sizes (<300 g/mol). Among the fluorophores was discovered a highly fluorogenic fluorophore with a unique turn-on property, 1, and it was developed into a washing-free bioprobe for visualizing cellular lipid droplets in living cells. Furthermore, motivated by the core’s compact size and structural analogy to indole, unprecedented tryptophan-analogous fluorogenic unnatural amino acids were constructed and incorporated into fluorogenic peptide probes for monitoring peptide–protein interactions.