Self-Assembled Nanostructures Based on Activatable Red Fluorescent Dye for Site-Specific Protein Probing and Conformational Transition Detection

Abstract

Smart and versatile nanostructures have demonstrated their effectiveness for biomolecule analysis and show great potential in digging insights into the structural/functional relationships. Herein, a nanoscale molecular self-assembly was constructed for probing the site-specific recognition and conformational changes of human serum albumin (HSA) with tunable size and emission. A tetraphenylethylene derivative TPE-red-COOH was used as the building block for tailoring fluorescence-silent nanoparticles. The highly specific and sensitive response to HSA was witnessed by the fast turn-on of the red fluorescence and simultaneous disassembly of the nanostructures, whereas various endogenous biomolecules cannot induce such response. The mechanism investigation indicates that the combination of multiple noncovalent interactions is the driving force for disassembling and trapping TPE-red-COOH into HSA. The resultant restriction of intramolecular rotation of TPE-red-COOH in the hydrophobic cavity of HSA induces the significant red emission. By using the fluorescence activatable nanosensor as the structural indicator, the stepwise conformational transitions of HSA during denaturing and the partial refolding of subdomain IIA of HSA were facilely visualized. Benefiting from its activatable signaling, sensitivity, and simplicity, such molecular assembly provides a kind of soft nanomaterial for site-specific biomolecule probing and conformational transition detection concerning their structure, function, and biomedical characteristics.

Selective detection of human serum albumin by near infrared emissive fluorophores: Insights into structure-property relationship

“…The intensity of emission decreases if a ligand is present in the site. 46 In our study, upon gradual addition of 1 in HSA, the emission intensity of the residue decreased. Addition of 0.4 equivalent of 1 quenched the emission up to ~30%.…”

Reducing aggregation caused quenching effect through co-assembly of PAH chromophores and molecular barriers

“…These examples include, controlling the molecular stacking to form J -aggregates, decreasing the crystalline degree via introducing amorphous domains, avoiding a slow intersystem crossing (ISC) process and controlling triplet formation 25–28 , and attaching long alkyl chain substitution onto chromophores to prevent π–π interaction between conjugated planes in aggregate states 29 . Very recently, a variety of fluorescent materials with famous aggregation-induced emission (AIE) properties have been prepared and widely used in many fields 4–7,29–33 . However, there are still severe problems remaining in above-mentioned methods.…”

Aptamer-Decorated Self-Assembled Aggregation-Induced Emission Organic Dots for Cancer Cell Targeting and Imaging

“…Tang et al reported a kind of propeller-shaped molecules like hexaphenylsilole and tetraphenylethylene with aggregation-induced emission (AIE) characteristics, in which the AIE luminogens (AIEgens) generally exhibit no or weak emission in solution but enhanced emission in aggregated or solid states . Since then, a variety of AIEgens have been developed. − More importantly, the strong solid-state emission of AIEgens provides great opportunity for fabricating highly bright organic nanoparticles (denoted as AIE dots) without destructing their emission. − …”