Abstract：
:The use of methanethiosulfonates as thiol-specific modifying reagents in the strategy of combined site-directed mutagenesis and chemical modification allows virtually unlimited opportunities for creating new protein surface environments. As a consequence of our interest in electrostatic manipulation as a means of tailoring enzyme activity and specificity, we have recently adopted this approach for the controlled incorporation of multiple negative charges at single sites in the representative serine protease, subtilisin Bacillus lentus (SBL). We now describe the use of this strategy to introduce multiple positive charges. A series of mono-, di- and triammonium methanethiosulfonates were synthesized and used to modify cysteine mutants of SBL at positions 62 in the S2 site, 156 and 166 in the S1 site and 217 in the S1' site. Kinetic parameters for these chemically modified mutants (CMM) enzymes were determined at pH 8.6. The presence of up to three positive charges in the S1, S1' and S2 subsites of SBL resulted in up to 77-fold lowered activity, possibly due to interference with the histidinium ion formed in the transition state of the hydrolytic reactions catalyzed.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Davis BG,Khumtaveeporn K,Bott RR,Jones JBdoi
10.1016/s0968-0896(99)00168-6subject
Has Abstractpub_date
1999-11-01 00:00:00pages
2303-11issue
11eissn
0968-0896issn
1464-3391pii
S0968-0896(99)00168-6journal_volume
7pub_type
杂志文章abstract：:Twenty-eight tetraketones (1-28) with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors. Remarkably compounds 25 (IC(50)=2.06 microM), 11 (IC(50)=2.09 microM), 15 (IC(50)=2.61 microM), and 27 (IC(50)=3.19 microM) were found to be the most active compounds of the series, even better t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.08.029
更新日期：2006-01-15 00:00:00
abstract：:The blending of key structural features from the purine and pyrimidine nucleobase scaffolds gives rise to a new class of hybrid nucleosides. The purine-pyrimidine hybrid nucleosides can be viewed as either N-3 ribosylated purines or 5,6-disubstituted pyrimidines, thus recognition by both purine- and pyrimidine-metabol...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.06.039
更新日期：2009-08-01 00:00:00
abstract：:We efficiently synthesized 2'-O,4'-C-aminomethylene-bridged nucleic acid (2',4'-BNANC) monomers bearing the four nucleobases, guanine, adenine, thymine, and 5-methylcytosine and incorporated these monomers into oligonucleotides. Initially, we carried out the transglycosylation reaction on several 2'-O-substituted 5-me...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.02.034
更新日期：2019-04-15 00:00:00
abstract：:Inhibition of the isoforms of nitric oxide synthase (NOS) has important applications in therapy of several diseases, including cancer. Using 1400 W [N-(3-aminomethylbenzyl)acetamidine], thiocitrulline and N(delta)-(4,5-dihydrothiazol-2-yl)ornithine as lead compounds, series of N-benzyl- and N-phenyl-2-amino-4,5-dihydr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(03)00451-6
更新日期：2003-09-15 00:00:00
abstract：:Abnormal β-amyloid peptide accumulation and aggregation is considered to be responsible for the formation and cerebral deposition of senile plaques in the brains of patients with Alzheimer's disease (AD). Inhibition of the formation of β-amyloid (Aβ) fibrils would be an attractive therapeutic target for the treatment ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.04.001
更新日期：2011-05-15 00:00:00
abstract：:A series of (2E,2'E)-1,1'-(3-hydroxy-5-methylbiphenyl-2,6-diyl)-bis(3-pheylprop-2-ene-1-ones (5-33) were prepared by the reaction of 1,3-diacetyl biphenyls (1-4) with different aldehydes in presence of catalytic amount of solid KOH in ethanol in excellent yields. The compounds were evaluated for anticancer activity ag...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.05.015
更新日期：2010-07-01 00:00:00
abstract：:5-HT(3A) receptor antagonists have been used mainly for the treatment of nausea and vomiting. These days, the antagonists are of special interest due to their therapeutic potential to treat other diseases such as depression, psychotic disorder, drug abuse, and irritable bowel syndrome. To discover novel 5-HT(3A) recep...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.04.029
更新日期：2009-07-01 00:00:00
abstract：:Chagas disease is an infection caused by protozoan Trypanosoma cruzi, which affects approximately 8-10million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases of Chagas disease; however, it has poor efficacy during the symptomatic chronic phase. Th...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.10.048
更新日期：2015-12-01 00:00:00
abstract：:A series of N'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3H-benzo[d]imidazole-5-carbohydrazide derivatives were synthesized and investigated for their abilities to inhibit β-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent Plasmodium berghei. Selected analogues ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.01.050
更新日期：2011-03-15 00:00:00
abstract：:D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D3 receptors. The new tracers 4...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.06.055
更新日期：2005-11-15 00:00:00
abstract：:A chemoenzymatic glycosylation remodeling method for the synthesis of selectively fluorinated glycoproteins is described. The method consists of chemical synthesis of a fluoroglycan oxazoline and its use as donor substrate for endoglycosidase (ENGase)-catalyzed transglycosylation to a GlcNAc-protein to form a homogene...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.03.009
更新日期：2013-08-15 00:00:00
abstract：:Investigation of the bark of Croton eluteria Bennett for biologically active compounds has led to the isolation of the new prenylbisabolane 3, whose structure was assessed by spectroscopic methods. The corresponding known enone 4 and the eudesmane sesquiterpene 2 were also obtained. Compound 3 proved active in selecti...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.04.025
更新日期：2005-07-01 00:00:00
abstract：:The toxicity of the molecules currently used in the treatment of human cytomegalovirus (HCMV) in immunocompromised hosts often causes interruption of the therapy. Cyclodextrins (Cds), oligosaccharides possessing a hydrophobic cavity, have the property of forming inclusion complexes with a great number of molecules, im...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)00247-9
更新日期：2001-02-01 00:00:00
abstract：:A new heterocyclic family of (2-(dimethylamino)ethyl)-2-substituted phenylnaphtho[2,1-d]thiazole-5-carboxamides modified from naphthalimides was designed, synthesized, and quantitatively evaluated as antitumor agents and photonucleases. All these compounds were found to be more cytotoxic against P388 than against A549...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.02.045
更新日期：2005-05-02 00:00:00
abstract：:A number of isosteres (oxadiazoles, thiadiazoles, tetrazoles and diazines) of benzocaine were prepared and evaluated for their capacity to induce methemoglobinemia-with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (met...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2014.02.013
更新日期：2014-04-01 00:00:00
abstract：:The cells of Bacillus stearothermophilus contain an NADH-dependent diacetyl (acetoin) reductase. The enzyme was easily purified to homogeneity, partially characterised, and found to be composed of two subunits with the same molecular weight. In the presence of NADH, it catalyses the stereospecific reduction of diacety...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/0968-0896(96)00086-7
更新日期：1996-08-01 00:00:00
abstract：:A series of novel benzimidazole derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the HepG2.2.15 cell line. The preliminary SAR was discussed. Compound 12a, with IC50<0.41 microM and SI>81.2, was the most promising compound and selected as the benchmark comp...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.05.076
更新日期：2010-07-15 00:00:00
abstract：:Synthesized series of cage dimeric 1,4-dihydropyridines have been systematically evaluated as MDR modulators in in vitro assays to investigate structure-dependent selectivity properties of inhibiting most cancer-relevant efflux pump proteins. Structure-activity relationships of each P-glycoprotein (P-gp) and multidrug...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.06.004
更新日期：2010-07-15 00:00:00
abstract：:A series of 10 new 5-[2-(substituted sulfamoyl)-4,5-dimethoxy-benzyl]-4aryl-s-triazole-3-thiones were synthesized and evaluated for in vitro antifungal and antibacterial activity. All compounds tested showed significant antifungal activity against all the micromycetes, compared to the commercial fungicide bifonazole. ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.10.082
更新日期：2008-02-01 00:00:00
abstract：:The solution-phase parallel synthesis involving reactions of Baylis-Hillman products of 3-substituted-5-isoxazolecarbaldehydes with nucleophiles and their in vivo antithrombotic evaluations are described along with the results of in vitro platelet aggregation inhibition assay of a few compounds. Results of the detaile...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.02.023
更新日期：2004-05-01 00:00:00
abstract：:Cells have evolved complex biochemical pathways for DNA interstrand crosslink (ICL) removal. Despite the chemotherapeutic importance of ICL repair, there have been few attempts to identify which mechanistic DNA repair inhibitor actually inhibits ICL repair. To identify such compounds, a new and robust ICL repair assay...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.09.045
更新日期：2015-11-01 00:00:00
abstract：:Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N(1) and N(2)) in the P-gp inhibitor XR9576 ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.03.014
更新日期：2007-06-01 00:00:00
abstract：:We have used fluorescence anisotropy to measure in situ the thermodynamics of binding of alanine-rich mutants of the GCN4 basic region/leucine zipper (bZIP) to short DNA duplexes, in which thymines were replaced with uracils, in order to quantify the contributions of the C5 methyl group on thymines with alanine methyl...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(01)00216-4
更新日期：2001-09-01 00:00:00
abstract：:Betulinic acid (BA), a pentacyclic triterpenoid, exhibits broad spectrum antiproliferative activity, but generally with only modest potency. To improve BA's pharmacological properties, fluorine was introduced as a single atom at C-2, creating two diastereomers, or in a trifluoromethyl group at C-3. We evaluated the im...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.05.016
更新日期：2019-07-01 00:00:00
abstract：:The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.04.006
更新日期：2004-06-15 00:00:00
abstract：:The substitution of the sterically hindered carbon of the potent thyroid hormone agonist, GC-1, was effected by a reaction based on the solvolysis of the benzylic hydroxyl group. The reaction was found to proceed in high yield with a variety of nucleophiles including alcohols, thiols, allyl silanes and electron-rich a...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00085-6
更新日期：1998-08-01 00:00:00
abstract：:A new brassinolide inhibitor, named KM-01, was isolated from the culture filtrates of two fungal species, Drechslera avenae and Pycnoporus coccineus, and the structure with absolute stereochemistry was elucidated as the fatty acid ester of an eremophilane sesquiterpene, bipolaroxin, based on spectroscopic analysis, ch...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00088-1
更新日期：1998-11-01 00:00:00
abstract：:The synthesis of a neoglycopeptide building block is described. The key step is a cycloaddition where the chemistry is orthogonal to standard glycosyl transfer methodology. Also described is some exploratory chemistry of the building block. ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(03)00182-2
更新日期：2003-07-03 00:00:00
abstract：:Allergic diseases are hypersensitivity disorders associated with the production of specific immunoglobulin E (IgE) to environmental allergens. Interleukin (IL)-4, produced primarily by CD4(+) T cells, is an important stimulus for the switch of the antibody isotype to IgE in both mice and humans. In this study we inves...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.01.027
更新日期：2005-04-01 00:00:00
abstract：:Twelve thiorhodamine derivatives have been examined for their ability to stimulate the ATPase activity of purified human P-glycoprotein (P-gp)-His(10), to promote uptake of calcein AM and vinblastine into multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their rates of transport in monolayers of mult...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.05.075
更新日期：2012-07-15 00:00:00
