The unique tripeptide structure of green fluorescent
protein (GFP),
a Ser-Tyr-Gly motif, generates the mature chromophore in situ to define
the emission profiles of GFP. Here, we describe the rational design
and discovery of a biomimetic fluorescent emitter, MBP, by mimicking
the key structure of the Ser-Tyr-Gly motif. Through systematically
tailoring the tripeptide, a family of four chromophores were engineered,
while only MBP exhibited bright fluorescence in different fluid solvents
with highly enhanced quantum yields. Distinct to previous hydrogen-bonding-induced
fluorescence quenching of GFP chromophore analogues, the emission
of MBP was only slightly decreased in protic solvents. Heteronuclear
multiple bond correlation techniques demonstrated the fundamental
mechanism for enhanced fluorescence emission owing to the synergy
of the formation of the intramolecular hydrogen-bonding-ring structure
and the self-restricted effect, which was further illustrated via
theoretical calculations. This work puts forward an extraordinary
approach toward highly emissive biomimicking fluorophores, which gives
new insights into the emission mechanisms and photophysics of GFP-like
chromophores.
Commercial gadolinium (Gd)-based contrast agents (GBCAs) play important role in clinical diagnostic of hepatocellular carcinoma, but their diagnostic efficacy remained improved. As small molecules, the imaging contrast and window of GBCAs is limited by low liver targeting and retention. Herein, we developed a liver-targeting gadolinium (Ⅲ) chelated macromolecular MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan, namely, CS-Ga-(Gd-DTPA)n, to improve hepatocyte uptake and liver retention. Compared to Gd-DTPA and non-specific macromolecular agent CS-(Gd-DTPA)n, CS-Ga-(Gd-DTPA)n showed higher hepatocyte uptake, excellent cell and blood biocompatibility in vitro. Furthermore, CS-Ga-(Gd-DTPA)n also exhibited higher relaxivity in vitro, prolonged retention and better T1-weighted signal enhancement in liver. At 10 days post-injection of CS-Ga-(Gd-DTPA)n at a dose of 0.03 mM Gd/Kg, Gd had a little accumulation in liver with no liver function damage. The good performance of CS-Ga-(Gd-DTPA)n gives great confidence in developing liver-specifc MRI contrast agents for clinical translation.
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