1.Cell-trappable quinoline-derivatized fluoresceins for selective and reversible biological Zn(II) detection.
McQuade LE1, Lippard SJ. Inorg Chem. 2010 Oct 18;49(20):9535-45. doi: 10.1021/ic1012507.
The synthesis and spectroscopic characterization of two new, cell-trappable fluorescent probes for Zn(II) are presented. These probes, 2-(4,5-bis(((6-(2-ethoxy-2-oxoethoxy)quinolin-8-yl)amino)methyl)-6-hydroxy-3-oxo-3H-8 xanthen-9-yl)benzoic acid (QZ2E) and 2,2'-((8,8'-(((9-(2-carboxyphenyl)-6-hydroxy-3-oxo-3H-xanthene-4,5-diyl)bis(methylene))bis(azanediyl))bis(quinoline-8,6-diyl))bis(oxy))diacetic acid (QZ2A), are poorly emissive in the off-state but exhibit dramatic increases in fluorescence upon Zn(II) binding (120 ± 10-fold for QZ2E, 30 ± 7-fold for QZ2A). This binding is selective for Zn(II) over other biologically relevant metal cations, toxic heavy metals, and most first-row transition metals and is of appropriate affinity (K(d1)(QZ2E) = 150 ± 100 μM, K(d2)(QZ2E) = 3.5 ± 0.1 mM, K(d1)(QZ2A) = 220 ± 30 μM, K(d2)(QZ2A) = 160 ± 80 μM, K(d3)(QZ2A) = 9 ± 6 μM) to reversibly bind Zn(II) at physiological levels. In live cells, QZ2E localizes to the Gogli apparatus where it can detect Zn(II).
2.Ibotenic acid analogues. Synthesis and biological and in vitro activity of conformationally restricted agonists at central excitatory amino acid receptors.
Krogsgaard-Larsen P, Nielsen EO, Curtis DR. J Med Chem. 1984 May;27(5):585-91.
A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. The excitatory effects of the 3- isoxazolol amino acids (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5, 4-c]pyridine-7-carboxylic acid (4, 7- HPCA ), (RS)-alpha-amino-3-hydroxy-5,6-dihydro-4H- cyclohept [1,2-d] isoxa zole - 8-propionic acid (8, 8- AHCP ), (RS)-alpha-amino-3- hydroxy-7,8-dihydro-6H- cyclohept [1,2-d] isoxazole -4-propionic acid (12, 4- AHCP ), and (RS)-alpha-(methylamino)-3-hydroxy-5-methyl- 4- isoxazolepropionic acid (15, N-Me-AMPA) were shown to be sensitive to (S)-glutamic acid diethyl ester (GDEE), an antagonist at quisqualic acid ( QUIS ) receptors, and insensitive to (RS)-2-amino-5-phosphonovaleric acid ( 2APV ), an antagonist at N-methyl-(R)-aspartic acid (NMDA) receptors.
3.Aromatic retinoic acid analogues. Synthesis and pharmacological activity.
Dawson MI, Hobbs PD, Chan RL, Chao WR, Fung VA. J Med Chem. 1981 May;24(5):583-92.
Aromatic analogues of (all-E)- and 13(Z)-retinoic acids have been synthesized as potential chemopreventive agents for the treatment of epithelial cancer. In the E series, (1E,3E)-1-(4-carboxyphenyl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3- butadiene (7a), its ethyl ester 5a, and the epoxy ethyl ester 14 displayed excellent activity in the assay for the inhibition of tumor promotor-induced mouse epidermal ornithine decarboxylase, while (1E,3E)-1-(4-carboethoxy-3-methylphenyl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3-butadiene (5b) was inactive. The 13(Z) analogues, (E)-1-(2-carboxyphenyl)-4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5-he xatriene (19) and (E)-1-(2-hydroxyphenyl)-4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5-he xatriene (27), had minimal activity.
4.Identification of the general acid/base catalyst of a family 3 beta-glucosidase from Flavobacterium meningosepticum.
Li YK1, Chir J, Tanaka S, Chen FY. Biochemistry. 2002 Feb 26;41(8):2751-9.
beta-Glucosidase from Flavobacterium meningosepticum (Fbgl) (also known as Chryseobacterium meningosepticum) has been classified as a member of the family 3 glycohydrolases. It is a retaining enzyme involving a two-step, double-displacement mechanism. D247 was shown to function as the nucleophile of the enzymatic reaction [Li, Y.-K., Chir, J., and Chen, F.-Y. (2001) Biochem. J. 355, 835-840]. However, the general acid/base catalyst of this enzyme and of all other family 3 glycohydrolases has not yet been identified. On the basis of amino acid sequence alignment of 15 family 3 enzymes, 11 residues (D71, R129, E132, E136, D137, K168, H169, E177, D247, D458, and E473) are highly conserved. All of these residues are studied by site-directed mutagenesis and kinetic investigation. Analyzing the catalytic power of all mutants reveals E473 residue is the best candidate of the acid/base catalyst. Detailed studies supporting this suggestion are summarized as follows.