Abstract:
:Nuclear magnetic resonance (NMR) spectroscopy is a valuable technique for ligand screening, because it exhibits high specificity toward chemical structure and interactions. Dissolution dynamic nuclear polarization (DNP) is a recent advance in NMR methodology that enables the creation of non-equilibrium spin states, which can dramatically increase NMR sensitivity. Here, the transfer of such spin polarization from hyperpolarized ligand to protein is observed. Mixing hyperpolarized benzamidine with the serine protease trypsin, a "fingerprint" of enhanced protein signals is observed, which shows a different intensity profile than the equilibrium NMR spectrum of the protein, but coincides closely to the frequency profile of a saturation transfer difference (STD) NMR experiment. The DNP experiment benefits from hyperpolarization and enables observation of all frequencies in a single, rapid experiment. Based on these merits, it is an interesting alternative to the widely used STD experiment for identification of protein-ligand interactions.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Min H,Sekar G,Hilty Cdoi
10.1002/cmdc.201500241subject
Has Abstractpub_date
2015-09-01 00:00:00pages
1559-63issue
9eissn
1860-7179issn
1860-7187journal_volume
10pub_type
杂志文章相关文献
ChemMedChem文献大全abstract::Tau-tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine kinase that putatively phosphorylates residues including S422 in tau protein. Hyperphosphorylation of tau protein is the primary cause of tau pathology and neuronal death associated with Alzheimer's disease. A library of 12 truncation variants comprising the ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300274
更新日期:2013-11-01 00:00:00
abstract::Cyclic RGD-containing functionalized azabicycloalkane peptides were synthesized with the aim of developing high-affinity selective integrin ligands as carriers for therapeutic and diagnostic purposes. Herein we describe the synthesis and in vitro screening of these RGD derivatives, as well as the determination of thei...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800422
更新日期:2009-04-01 00:00:00
abstract::The concise synthesis and structure-activity relationship (SAR) studies of 3-aroylindoles were carried out in an effort to improve the potency and solubility of anticancer drug candidate BPR0L075 (8) by exploring structure modifications through three regimens: substitution of the B ring, at the N1 position, and of the...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200600125
更新日期:2006-10-01 00:00:00
abstract::Herein we report the design, synthesis, X-ray structural, and biological studies of an exceptionally potent HIV-1 protease inhibitor, compound 5 ((3S,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl ((2S,3R)-4-((2-(cyclopropylamino)-N-isobutylbenzo[d]thiazole)-6-sulfonamido)-1-(3,5-difluorophenyl)-3-hydroxybutan-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700824
更新日期:2018-04-23 00:00:00
abstract::The in silico design, synthesis, and biological evaluation of ten potent type II dehydroquinase inhibitors are described. These compounds contain an anhydroquinate core, incorporated as a mimic of the enolate reaction intermediate. This substructure is attached by a variety of linking units to a terminal phenyl group ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700032
更新日期:2007-07-01 00:00:00
abstract::The application of covalent inhibitors has experienced a renaissance within drug discovery programs in the last decade. To leverage the superior potency and drug target residence time of covalent inhibitors, there have been extensive efforts to develop highly specific covalent modifications to decrease off-target liab...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800592
更新日期:2018-12-06 00:00:00
abstract::Natural products containing the α,β-unsaturated δ-lactone skeleton have been shown to possess a variety of biological activities. The natural product (-)-tarchonanthuslactone (1) possessing this privileged scaffold is a popular synthetic target, but its biological activity remains underexplored. Herein, the total synt...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500246
更新日期:2015-10-01 00:00:00
abstract::Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1-benzyl-4-piperidyl)[6,7-dimethoxy-2-(4-methyl-1,4-diazepin-1-yl)-4-quinazolinyl]amine (BIX01294; 1), a known...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402098
更新日期:2014-10-01 00:00:00
abstract::P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402463
更新日期:2015-02-01 00:00:00
abstract::The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201700113
更新日期:2017-05-09 00:00:00
abstract::The synthesis of SCF3 as well as SeCF3 isosteres of two OCF3 -containing drugs was achieved through visible light and copper-catalyzed processes. Herein, we show that chalcogen replacement modulates physicochemical and ADME properties without introducing intrinsic liabilities. The SCF3 and SeCF3 groups are more lipoph...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900452
更新日期:2019-09-04 00:00:00
abstract::Herein we propose the D-Trp-Phe sequence within an inverse type II β-turn as a new kind of pharmacophoric motif for μ-opioid receptor (MOR) cyclopeptide agonists. Initially, we observed that c[Tyr-D-Pro-D-Trp-Phe-Gly] (4), an analogue of endomorphin-1 (H-Tyr-Pro-Trp-Phe-NH₂) lacking the crucial protonatable amino grou...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100169
更新日期:2011-09-05 00:00:00
abstract::Selective inhibitors of the protein tyrosine phosphatase SHP2 (src homology region 2 domain phosphatase; PTPN11), an enzyme that is deregulated in numerous human tumors, were generated through a combination of chemical synthesis and structure-based rational design. Seventy pyridazolon-4-ylidenehydrazinyl benzenesulfon...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500015
更新日期:2015-05-01 00:00:00
abstract::Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1'-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124 I isotope). The PET imaging ability and ex vivo biodistribution of [124 I]4 were compared with t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900352
更新日期:2019-08-20 00:00:00
abstract::Prodrugs are effective tools in overcoming drawbacks typically associated with drug formulation and delivery. Those employing esterase-triggered functional groups are frequently utilized to mask polar carboxylic acids and phenols, increasing drug-like properties such as lipophilicity. Herein we detail a comprehensive ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300255
更新日期:2013-10-01 00:00:00
abstract::3,6-Dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide derivatives were synthesized, and their structures were confirmed by single-crystal X-ray diffraction. This reaction yields the 1,4-dicarboxamide derivatives rather than the 1,2-dicarboxamide derivatives. Their in vitro antitumor activities were evaluated against SGC-79...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200109
更新日期:2012-06-01 00:00:00
abstract::Salecan is a water-soluble bacterial polysaccharide consisting of glucopyranosyl units linked by α-1,3 and β-1,3 glycosidic bonds. salecan is suitable for the development of hydrogels for biomedical applications, given its outstanding physicochemical and biological profiles. In this study we designed a new semi-interp...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600570
更新日期:2017-01-20 00:00:00
abstract::Targeted structural modifications have led to a novel type of buprenorphine-derived opioid receptor ligand displaying an improved selectivity profile for the μ-OR subtype. On this basis, it is shown that phenylazocarboxamides may serve as useful bioisosteric replacements for the widely occurring cinnamide units, witho...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000180
更新日期:2020-07-03 00:00:00
abstract::(±)-6-Alkyl-2,4-diaminopyrimidine-based inhibitors of bacterial dihydrofolate reductase (DHFR) have been prepared and evaluated for biological potency against Bacillus anthracis and Staphylococcus aureus. Biological studies revealed attenuated activity relative to earlier structures lacking substitution at C6 of the d...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200291
更新日期:2012-11-01 00:00:00
abstract::From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines. The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and n...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200403
更新日期:2013-02-01 00:00:00
abstract::Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin-derived compounds, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), in an attempt to...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000482
更新日期:2011-03-07 00:00:00
abstract::Targeting the biosynthetic pathway of neuroactive steroids with specific 18 kDa translocator protein (TSPO) ligands may be a viable therapeutic approach for a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between binding affinity and in vitro steroidogenic efficacy has li...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700220
更新日期:2017-08-22 00:00:00
abstract::Steroid derivatives bearing fluorescent groups such as anthracene, dansyl, deazaflavin, and pyrene attached to C6 were synthesized. These compounds are unique inhibitors of cytochrome P450 3A4 (CYP3A4) and display similar IC(50) values in the microM range for the CYP3A4 substrates midazolam, testosterone, and nifedipi...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200600300
更新日期:2007-05-01 00:00:00
abstract::Cancer cells express high levels of CK2, and its inhibition leads to apoptosis. CK2 has therefore emerged as a new drug target for cancer therapy. A biligand inhibitor ARC-772 was constructed by conjugating 4-(2-amino-1,3-thiazol-5-yl)benzoic acid and a carboxylate-rich peptoid. ARC-772 was found to bind CK2 with a Kd...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700457
更新日期:2017-10-20 00:00:00
abstract::TIBO- and TBO-like sulfone derivatives 1 and 2 were designed, synthesized, and tested for their ability to block the replication cycle of HIV-1 in infected cells. The anti-HIV-1 activities of sulfones 3, which were intermediates in the syntheses of 1 and 2, were also evaluated. Surprisingly, the sulfone analogues of T...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200500020
更新日期:2006-01-01 00:00:00
abstract::Meridional rhodium(III) polypyridyl complexes of the type mer-[RhX(3)(DMSO)(pp)] (X=Cl, pp=phen 1, dpq 2, dppz 3; X=Br, pp=phen 4) represent a promising class of potent cytostatic agents for the treatment of lymphoma and leukemia. Exposure of their DMSO solutions to light leads to slow isomerization to mixtures of the...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800311
更新日期:2009-02-01 00:00:00
abstract::Because only a few studies have investigated the affinity and functional activity of NMDA receptor open channel blockers under the same assay conditions, a comparative study of common open channel blockers is of major interest. The pharmacological activities of MK-801, phencyclidine (PCP), dexoxadrol, etoxadrol, (S)- ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700810
更新日期:2018-03-06 00:00:00
abstract::Platinum amidine complexes represent a new class of potential antitumor drugs that contain the imino moiety HN=C(sp(2)) bonded to the platinum center. They can be related to the iminoether derivatives, which were recently shown to be the first Pt(II) compounds with a trans configuration endowed with anticancer activit...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201100150
更新日期:2011-07-04 00:00:00
abstract::Cellular chaperones that belong to the heat-shock protein 90 (Hsp90) family are a prerequisite for successful viral propagation for most viruses. The hepatitis C virus (HCV) uses Hsp90 for maturation, folding, and modification of viral proteins. Based on our previous discovery that marine alkaloid analogues with a 4,5...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800724
更新日期:2019-02-05 00:00:00
abstract::We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moie...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000305
更新日期:2010-12-03 00:00:00