Biomedical subjects
Publications and source records attributed to Young-Tae Chang.
The first fluorescent styryl dye library with a broad color range was synthesized by combinatorial condensation of various aldehydes and methyl pyridinium compounds, and their applications as organelle specific staining probes were demonstrated.
[reaction: see text] To improve upon the previous orthogonal method for synthesis of a triazine library, an alternative strategy has been developed via oxidation-activation of the thioether to the sulfone. Through a comparison between these two methods, the sulfone strategy was demonstrated as an enhanced method in the generation of highly pure triazine library compounds.
Solid-phase organic synthesis (SPOS) has an ever-expanding role in the field of organic synthesis. Partially out of difficulty, and partially from the rapid speed of progress, few basic studies on the role of the physical structure of the resin have been undertaken, and the dissemination of the existing knowledge has been slow. Major advances have been made in the understanding of the many factors that govern a SPOS reaction's performance as a function of the choice of solid support.
As the human genome sequence is nearly deciphered, it is important to turn the attention to the physiological functions of the genes. Thus, the study of the gene products, the proteins, is the next big challenge. The proteins, however, are not the final gene products in many cases. It has been shown that carbohydrates participate in post-translational modifications and in many other functional regulations, hence the study of the glycome, the entire collection of carbohydrates is essential in order to determine the functions of all genes, and will greatly enhance the field of chemical genetics. Known biological function / targets of carbohydrates and combinatorial synthesis & structural analysis of natural / non-natural carbohydrates are surveyed in this review. Methods to search for new biological targets that include carbohydrate mimetics and carbohydrate scaffolds along with chip technology, are also presented.
The first orthogonal combinatorial synthesis of a high-purity triazine library was demonstrated. Novel triazine-based microtubule inhibitors were discovered by an efficient zebrafish embryo screening and in vitro microtubule polymerization assay.
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Since the discovery of D-myo-inositol 1,4,5-trisphosphate, which plays a pivotal role as a second messenger in transmembrane signaling, the scope of the phosphoinositide-based signaling processes has been continually expanding. However, the clear understanding of the molecular signal transduction mechanisms including the functions of newly found IP(n) is still lacking. As a continuing effort to our previously reported syntheses of all possible 39 optically inactive regioisomers of myo-inositol phosphates (IP(n); n = 1-6), we synthesized all possible optically active regioisomers of myo-IP(3) and myo-IP(4) using chiral IBz(3)s and IBz(2)s, respectively. A series of procedures involving CRL-catalyzed enzymatic resolution of racemic 1,2:5,6-di-O-isopropylidene-myo-inositol and base-catalyzed benzoyl migration in tri- and dibenzoyl-isopropylidene-myo-inositol afforded eight enantiomeric pairs of IBz(3) and six enantiomeric pairs of IBz(2), respectively. Phosphorylation of these intermediates by the phosphitylation and oxidation procedure gave the target products.
A facile synthesis of a combinatorial ceramide library and their activities in the NF-kappaB pathway and in apoptosis induction/prevention were demonstrated. A novel NF-kappaB activating molecule was discovered among ceramide containing beta-galactose, and the structural requirements of ceramides for apoptosis induction was elucidated.
A simple and practical synthetic procedure for the versatile intermediates, (+/-)-1,2:5,6-di-O-isopropylidene-myo-inositol and (+/-)-6-O-benzoyl-1,2:4,5-di-O-isopropylidene-myo-inositol, is described.
Using a muscle cell differentiation screen, we have identified myoseverin from a 2,6,9-trisubsituted purine library as a purine-based microtubule binding molecule [1]. Structure-activity relation studies of myoseverin identify positions N2 and N6 to be critical for inhibiting muscle differentiation. Inhibition of microtubule polymerization induced the reversion of terminally differentiated myotubes to mononucleated cells that were responsive to both growth and differentiation conditions, without any observable cytotoxicity. Comparison of myoseverin derivatives to taxol, vinblastine, nocodazole, and colchicine identify myoseverin's effect as being selectively reversible in addition to lacking the cytotoxic effects of these non-purine-based microtubule-disrupting molecules. Myoseverin, as a purine-based microtubule inhibitor, reverted terminal muscle-differentiated cells to a state that was responsive to environmental cues. These results suggest that myoseverin may have applications in muscle regeneration and stem cell differentiation.
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.
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.
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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.