Drug Sensing Protein Crystals Doped with Luminescent Lanthanide Complexes

Abstract

Hen egg white lysozyme (HEWL) crystals are a model system for protein crystallization due to economical production and facile crystal growth. Here we grew small, rod-like HEWL crystals and proceeded with stepwise synthesis to dope the protein crystals with luminescent lanthanide complexes [(Eu­(TTA)3phen] (TTA = 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedionato, phen = 1,10-phenanthroline). Several compounds (coumarin, tinidazole, and acridine orange) were observed to quench the lanthanide complexes in solution or embedded within crystals. Coumarin is a precursor for anticoagulant drugs and tinidazole is used to combat bacterial or protozoan infections. In contrast, acridine orange is a widely used, versatile fluorescent dye used to stain acidic vacuoles, RNA, and DNA in living cells. These results suggest that protein crystals may provide a feasible matrix for entrapping luminescent species with practical biosensing applications.

Waste PET as a Reactant for Lanthanide MOF Synthesis and Application in Sensing of Picric Acid

“…There is a need to develop high sensitivity, easily prepared and quick response luminescent sensors for TNP. The luminescent Ln-MOFs and their inherent synthetic versatility seems to be promising for small molecular sensors [28,29].…”

Conditionally designed luminescent DNA crystals doped by Ln3+(Eu3+/Tb3+) complexes or fluorescent proteins with smart drug sensing property

“…These complexes have properties that differ from fluorescent proteins in interesting ways (e.g., a very large Stokes shift, long emission lifetime, etc.). Following our earlier work installing luminescent lanthanide complexes in protein crystals, 51,52 we used a similar approach here to synthesize luminescent complexes inside the crystals. After adding rare earth ions into the solution, the rare earth ions presumably diffused into the crystal pores, with no visible change to the crystals.…”

Diverse crystalline protein scaffolds through metal‐dependent polymorphism

“…Protein crystals, due to high protein concentration and precise order within the crystal, are increasingly recognized for the potential applications in drug delivery, vaccine development, catalysis, biosensing and even chromatography, far beyond the “traditional” role of structure determination (Abe & Ueno, 2015; Artusio et al, 2020; Contreras‐Montoya et al, 2019; Contreras‐Montoya et al, 2021; Fernandez‐Penas et al, 2021; Gavira et al, 2018; Hartje & Snow, 2019; Huber et al, 2018; Kowalski et al, 2019; Sun et al, 2019; Ward & Snow, 2020; Xu et al, 2021). Many applications would require crystal stabilization through chemical cross‐linking to prevent the material from dissolution when removed from the crystallization medium (Ayala et al, 2002; Hartje et al, 2018; Margolin & Navia, 2001; Noritomi et al, 1998; Quiocho & Richards, 1964; Yan et al, 2015), although dissolving crystals have been used for slow‐release drug delivery (Yang et al, 2003).…”