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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 approximately 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.

Two 60+-membered libraries of alpha-galactosylceramides have been prepared by reactions between activated ester resins and two core, fully deprotected galactosylated sphingoid bases. The libraries were evaluated for their ability to stimulate CD1d-restricted NKT cells, using in vitro stimulation of a murine NKT cell hybridoma line and for their ability to induce the expansion of NKT cells from peripheral blood mononuclear cells (PBMC) of a normal human subject. Our results showed that many compounds constructed on a C18-phytosphingosine base had significant stimulatory activity in both assays. Because no product purification was required, this approach is particularly attractive as a method for rapid synthesis of large libraries of potential immunomodulatory glycosylceramides.

The aminolysis of a novel activated ester resin was utilized for kinetic study via continuous in situ fluorescence measurements. A variety of resin compositions (polystyrene, JandaJel, ArgoPore, TentaGel, NovaGel, and PEGA) and solvents (dimethylformamide, acetonitrile, tetrahydrofuran, 1,2-dichlorethane, and toluene) were tested to compare their effects on the reaction rate. A linear relationship between the reaction rate and (solvent polarity x swelling of resin) was elucidated for the aminolysis reaction.

By a systematic ionic effect study in colorimetric dye arrays, we effectively suppressed the anion effect using the proper buffer condition and configured a universal cation sensor system. This result cast a warning for careful validation for other anion sensing systems in aqueous solution.

The diversity-oriented fluorescence library approach (DOFLA) has emerged and found applications in various fields to meet the acute demands for novel fluorescence sensors. The power of this approach has been demonstrated with the impressive discoveries of novel sensors for polymers such as DNA and heparin or for small molecules such as GTP and glutathione ( J. Am. Chem. Soc. 2003, 125, 1130- 1131 ; J. Am. Chem. Soc. 2006, 128, 10380- 10381 ; J. Am. Chem. Soc. 2007, 129, 4510- 4511 ; Chem. Commun. [Online early access]. DOI: 10.1039/b717058k. Published online Dec 11, 2008. http://www.rsc.org/publishing/journals/CC/article.asp?doi=b717058k ). Herein we report the application of this approach on quinaldinium fluorescent dye library synthesis on solid support and novel chymotrypsin sensor discovery. The new sensors are not only selective to chymotrypsin over other proteins but also only to the active conformation of chymotrypsin.

The combinatorial fluorescent dapoxyl dye library was prepared by both solution- and solid-phase synthesis, generating 80 unique dapoxyl derivatives. A fluorescence-based screening toward human serum albumin (HSA) found one highly sensitive HSA binder ( A41-S) with over 55-fold intensity change. Displacement assay showed the selective binding of A41-S to the site I of HSA, addressing its potential to be a highly selective and sensitive HSA probe.

A novel and highly diverse tagged triazine library incorporating a triethylene glycol-based linker was synthesized using an orthogonal combinatorial approach on the solid phase and covalently immobilized on a glass substrate as a small molecule microarray (SMM). The SMM was screened with a fluorophore-conjugated human IgG, and 4 novel binders from a library of 2688 compounds were identified from the fully spatially addressable array without the need for compound decoding. Using surface plasmon resonance (SPR) analysis, binding seen on the array was confirmed, and a binding constant as low as Kd = 2.02 x10(-6) M was measured.

A novel safety-catch method for orthogonal synthesis of highly pure trisubstituted triazines was developed. Since the polymer-support used in this method is not acid-labile, this strategy can be uniquely applied to the synthesis of acid-sensitive triazine library compounds. This method will dramatically increase the diversity of triazine and other related heterocyclic library compounds.

Novel nitrophenol solid supports based on various resin materials (polystyrene, TentaGel, macroporous, PEGA, and silica gel) are reported for facile amide and sulfonamide library synthesis. The broad choice of resin materials available will allow the reaction to occur successfully in solvents ranging from nonpolar organic solvents to aqueous media.