Principles, modulation, and applications of fluorescent protein chromophores

Fluorescent proteins (FPs) have gained much attention over the last few decades as powerful tools in bioimaging since the discovery of green fluorescent protein (GFP) in the 1960s. The mechanism of FP bioluminenscence has been well-studied, and new variants with improved photophysical properties are being constantly generated. In this review, a brief history of GFP along with its biogenesis is first provided. Next, the fluorescent and quenching mechanism governing the photophysical property of GFP is elaborated. Most importantly, we seek to introduce the expanding family of FP derivatives that mimics the chromophore core structure of FPs. Multiple physical and chemical strategies have been discussed to minimize the inherent fluorescence quenching effect of FP derivatives. Finally, we briefly overview the biological application of FP derivatives, with a focus on fluorescent RNA aptamer and recently reported protein aggregation detection probes. Through citing and discussing the most important works in this field, this review aims to provide a general photophysical understanding regarding the luminescence phenomenon of GFP and its derivatives, as well as chemical strategies to design functional FP derivatives.