Abstract:
:On-line affinity capillary electrophoresis-electrospray ionization-mass spectrometry (ACE-MS) was used for the simultaneous measurement of multiple binding constants of an all-D-tetrapeptide library to the model receptor, vancomycin. Determination of Kd values for the 19 peptides of the form Fmoc-DXYA is demonstrated. The data are compared with the results obtained for individual compounds using ACE-UV, and good correlation between the two detection methods is shown. Simultaneous determination of multiple Kd values by ACE-MS is achieved in one set of experiments, whereas only one Kd value can be obtained by ACE-UV during the same time. ACE-MS measures multiple binding constants in solution in a fast and reliable manner using femtomole amounts of samples.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Dunayevskiy YM,Lyubarskaya YV,Chu YH,Vouros P,Karger BLdoi
10.1021/jm970578ssubject
Has Abstractpub_date
1998-03-26 00:00:00pages
1201-4issue
7eissn
0022-2623issn
1520-4804pii
jm970578sjournal_volume
41pub_type
杂志文章abstract::To probe the space at the floor of the orthosteric ligand binding site in the dopamine D(1) receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8α-axial, 8β-equatorial, and 7α-equatorial were synthesized by photochemical cyclization of appropriat...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm200334c
更新日期:2011-08-11 00:00:00
abstract::The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00473
更新日期:2015-06-11 00:00:00
abstract::The perceived and actual burden of false positives in high-throughput screening has received considerable attention; however, few studies exist on the contributions of distinct mechanisms of nonspecific effects like chemical reactivity, assay signal interference, and colloidal aggregation. Here, we analyze the outcome...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm901070c
更新日期:2010-01-14 00:00:00
abstract::A series of N-benzylpiperidine benzisoxazoles has been developed as potent and selective inhibitors of the enzyme acetylcholinesterase (AChE). The benzisoxazole heterocycle was found to be an appropriate bioisosteric replacement for the benzoyl functionality present in the N-benzylpiperidine class of inhibitors. The t...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00043a012
更新日期:1994-08-19 00:00:00
abstract::In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00207a023
更新日期:1978-09-01 00:00:00
abstract::A diverse 5000-compound library was synthesized from commercially available diamines and screened for activity against Mycobacterium tuberculosis in vitro, revealing 143 hits with minimum inhibitory concentration (MIC) equal to or less than 12.5 microM. New prospective scaffolds with antitubercular activity derived fr...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm050948+
更新日期:2006-06-01 00:00:00
abstract::A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00151a003
更新日期:1986-01-01 00:00:00
abstract::The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high-re...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00058a010
更新日期:1993-03-19 00:00:00
abstract::Insulin secretion by pancreatic β-cells in response to glucose or other secretagogues is tightly coupled to membrane potential. Various studies have highlighted the prospect of enhancing insulin secretion in a glucose-dependent manner by blocking voltage-gated potassium channels (K(v)) and calcium-activated potassium ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm401904q
更新日期:2014-03-27 00:00:00
abstract::Condensation of cyanothioacetamide (4) with ethyl alpha-(ethoxymethylene)acetoacetate (5b), ethyl 4-ethoxy-2-(ethoxymethylene)-3-oxobutanoate (5c), ethyl 2-(ethoxymethylene)-3-oxo-4-phenylpropanoate (5d) afforded exclusively the corresponding 6-substituted pyridines (6b-d). Cyclization of 4 with 3-carbethoxybutane-2,4...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00401a023
更新日期:1988-06-01 00:00:00
abstract::USP7 is a promising target for cancer therapy as its inhibition is expected to decrease function of oncogenes, increase tumor suppressor function, and enhance immune function. Using a structure-based drug design strategy, a new class of reversible USP7 inhibitors has been identified that is highly potent in biochemica...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00245
更新日期:2020-05-28 00:00:00
abstract::We report analogues of N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Ilys-Pro-D-Ala- NH2, the parent antagonist (PA), which is a potent antagonist of LHRH. To simplify future radioactive labeling we prepared N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Arg-Pro-D-Ala-NH2 (4), [Arg8]PA, which had good activit...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00082a004
更新日期:1992-02-21 00:00:00
abstract::Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm1012006
更新日期:2011-01-13 00:00:00
abstract::4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00137a025
更新日期:1981-05-01 00:00:00
abstract::To better understand the difficulties surrounding the identification of novel antibacterial compounds from corporate screening collections, physical properties of ∼3200 antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501552x
更新日期:2014-12-11 00:00:00
abstract::Nonpeptidic chiral macrocycles were designed on the basis of an analogue of suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification of critical amino acid residues highly conserved in the cap region of HDACs guided the design of the subero...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm101092u
更新日期:2010-12-09 00:00:00
abstract::Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm020044d
更新日期:2002-11-07 00:00:00
abstract::9-acridinyl derivatives of 1,6-hexanediamine, 1,8-octanediamine, bis(3-aminopropyl)amine, N,N'-bis(3-amino-propyl)piperazine, and N-ethyl-1,6-hexanediamine in the form of their hydrochlorides were prepared in high yields and converted into potential hetero bis DNA intercalating diacridines. The corresponding potential...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00364a028
更新日期:1983-10-01 00:00:00
abstract::5-(Ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (ezutromid, 1) is a first-in-class utrophin modulator that has been evaluated in a phase 2 clinical study for the treatment of Duchenne muscular dystrophy (DMD). Ezutromid was found to undergo hepatic oxidation of its 2-naphthyl substituent to produce two regioisome...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b01547
更新日期:2020-03-12 00:00:00
abstract::Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polya...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm701198s
更新日期:2008-01-24 00:00:00
abstract::The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm060673d
更新日期:2006-10-05 00:00:00
abstract::4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm900290r
更新日期:2009-08-13 00:00:00
abstract::Amantadine inhibits the M2 proton channel of influenza A virus, yet its clinical use has been limited by the rapid emergence of amantadine-resistant virus strains. We have synthesized and characterized a series of polycyclic compounds designed as ring-contracted or ring-expanded analogues of amantadine. Inhibition of ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm101334y
更新日期:2011-04-28 00:00:00
abstract::A series of new amine cyanoborane derivatives were synthesized and exhibited antifungal activity. A long alkyl chain attached to the nitrogen of the amine cyanoboranes and carboxyboranes enhances antifungal activity. An enhanced activity was also obtained upon the halogenation of the amine cyanoboranes as well as in t...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm060476e
更新日期:2006-08-10 00:00:00
abstract::We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 (5), the derivative of MS I, potentiates ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b01511
更新日期:2019-11-14 00:00:00
abstract::The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC(50) = 6.1 ± 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallo...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm300334d
更新日期:2012-09-13 00:00:00
abstract::As a continuation of our project aimed at the search for new and safe chemotherapeutic and chemoprophylactic agents against American trypanosomiasis (Chagas' disease), several drugs structurally related to 4-phenoxyphenoxyethyl thiocyanate (4) were designed, synthesized, and evaluated as antiproliferative agents again...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0201518
更新日期:2002-08-29 00:00:00
abstract::A series of substituted analogues based on the novel 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-dione ring system have been synthesized and shown to exhibit antiinflammatory activity in the adjuvant-induced arthritis rat model (AAR). The activity exhibited by the pyrimidopurinediones in this model of chroni...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00125a029
更新日期:1989-05-01 00:00:00
abstract::To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of t...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049207j
更新日期:2005-02-24 00:00:00
abstract::The interesting bronchodilator activity of certain dl-11-deoxy-3-thiaprostaglandins and their preparation by the conjugate addition of appropriately substituted (E)-1-alkenyllithio cuprate reagents to requisite cyclopentenones are described. ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00222a024
更新日期:1977-12-01 00:00:00