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J. Comb. Chem. 2008, 10, 376–380
Article Selective Human Serum Albumin Sensor from the Screening of a Fluorescent Rosamine Library Young-Hoon Ahn,† Jun-Seok Lee,†,‡,§ and Young-Tae Chang*,†,‡,§,| Department of Chemistry, New York UniVersity, New York, New York 10003, Department of Chemistry and NUS MedChem Program of the Office of Life Sciences, National UniVersity of Singapore, Singapore 117543, and Laboratory of Bioimaging Probe DeVelopment, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore 138667 ReceiVed January 31, 2008 A fluorescent dye library approach for the development of a bioanalyte sensor was sought. The screening of a rosamine dye library against diverse macromolecules led to the discovery of a highly sensitive human serum albumin binder, G13, with ∼36-fold fluorescence intensity change. G13 showed a highly selective response to HSA over other macromolecules including albumins from other species. The potential use of G13 for the detection of HSA in biofluids is described. Introduction A small molecule fluorescent probe that detects a specific bioanalyte can provide lots of information including the dynamic monitoring of bioanalytes in a cellular context1 or selective detection and quantification of the analyte in a biosample.2 While many fluorescent probes have been designed individually by modulating the structural features to control a fluorescence property,3 a diversity oriented fluorescence library approach (DOFLA), where structurally and spectrally diverse fluorescent small molecules are synthesized and screened against a broad range of bioanalytes, has led to the discovery of many potential bioanalyte probe/sensors: for example, β-amyloid plaque and in vivo RNA probes from a styryl dye library,4 a GTP sensor from a benzimidazolium dye library,5 and an albumin binder from a dapoxyl dye library.6 Recently, our group has sought a fluorescent dye library with improved photophysical properties, and we have successfully constructed a library of rosamine derivatives (Figure 1).7 While both rhodamine and fluorescein carry a 2′carboxylic acid group, which plays a role in constraining the rotation of the 9-phenyl ring and thus modulating the fluorescence change in fluorescein,8 rosamine derivatives that lack the 2′-carboxylic acid group were envisioned to contain an increased flexibility (Figure 1) and thus were expected * To whom correspondence should be addressed. Phone: +65-6516-6774. Fax: +65-6779-1691. E-mail:
[email protected]. † Department of Chemistry, New York University. ‡ Department of Chemistry, National University of Singapore. § NUS MedChem Program of the Office of Life Sciences, National University of Singapore. | Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium.
to be potential sensor candidates in which fluorescence properties could be changed by a macromolecule binding event. Here we report the screening of a rosamine library against diverse macromolecules, leading to the discovery of a potential human serum albumin (HSA) sensor, G13, which shows a highly selective and sensitive response to HSA over other analytes. Serum albumin is the most abundant protein in blood plasma and plays a role in maintaining the osmotic pressure of the blood compartment and also in the transport and deposition of many endogenous and exogenous substances.9 The remarkably broad range of ligands binding to serum albumin, which results in a significant impact on the pharmacokinetics of drugs, have elicited high attention to this protein. Many studies have been directed toward the study of its binding sites10 and structural characterizations11 and also for the development of a specific and selective fluorescent binder.6,12 In particular, the detection of albumin has a clinical importance because its concentration in body fluids such as blood or urine is a reliable indicator of various diseases including liver or kidney disease, malnutrition, and microalbuminuria.12a,13 Although many fluorescent binders to HSA do exist, there is only one fluorescent probe that selectively detects albumin (albumin blue 580).12a Other fluorescent binders are mostly environmentally sensitive probes and have quite low excitation (
