Abstract:
:We previously described synapsin III (Syn III) as a synaptic phosphoprotein that controls dopamine release in cooperation with α-synuclein (aSyn). Moreover, we found that in Parkinson's disease (PD), Syn III also participates in aSyn aggregation and toxicity. Our recent observations point to threo-methylphenidate (MPH), a monoamine re-uptake inhibitor that efficiently counteracts the freezing-gait characteristic of advanced PD, as a ligand for Syn III. We have designed and synthesised two different fluorescently labelled MPH derivatives, one with Rhodamine Red (RHOD) and one with 5-carboxytetramethylrhodamine (TAMRA), to be used for assessing MPH binding to Syn III by FRET. TAMRA-MPH exhibited the ideal characteristics to be used as a FRET acceptor, as it was able to enter into the SK-N-SH cells and could interact specifically with human green fluorescent protein (GFP)-tagged Syn III but not with GFP alone. Moreover, the uptake of TAMRA-MPH and co-localization with Syn III was also observed in primary mesencephalic neurons. These findings support that MPH is a Syn III ligand and that TAMRA-conjugated drug molecules might be valuable tools to study drug-ligand interactions by FRET or to detect Syn III in cytological and histological samples.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Casiraghi A,Longhena F,Straniero V,Faustini G,Newman AH,Bellucci A,Valoti Edoi
10.1002/cmdc.202000128subject
Has Abstractpub_date
2020-07-20 00:00:00pages
1330-1337issue
14eissn
1860-7179issn
1860-7187journal_volume
15pub_type
杂志文章相关文献
ChemMedChem文献大全abstract::An emerging and attractive target for the treatment of Alzheimer's disease is to inhibit the aggregation of beta-amyloid protein (Abeta). We applied the retro-enantio concept to design an N-methylated peptidic inhibitor of the Abeta42 aggregation process. This inhibitor, inrD, as well as the corresponding all-L (inL) ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200900191
更新日期:2009-09-01 00:00:00
abstract::There has been significant interest in spleen tyrosine kinase (Syk) owing to its role in a number of disease states, including autoimmunity, inflammation, and cancer. Ongoing therapeutic programs have resulted in several compounds that are now in clinical use. Herein we report our optimization of the imidazopyrazine c...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500333
更新日期:2016-01-19 00:00:00
abstract::β-Alanyl-D-histidine (D-CAR, the enantiomer of the natural dipeptide carnosine) is a selective and potent sequestering agent of reactive carbonyl species (RCS) that is stable against carnosinase, but is poorly absorbed in the gastrointestinal tract. Herein we report a drug discovery approach aimed at increasing the or...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100042
更新日期:2011-07-04 00:00:00
abstract::A historical overview of key events that led, 50 years ago, to the foundation of the European Federation for Medicinal Chemistry (EFMC), and the impact this had on promoting and structuring medicinal chemistry as a discipline in Europe. EFMC, together with the growing number of newly established national medicinal che...
journal_title:ChemMedChem
pub_type: 社论
doi:10.1002/cmdc.202000691
更新日期:2020-12-15 00:00:00
abstract::A series of 1,3,3,4-tetrasubstituted pyrrolidine containing CCR5 receptor antagonists were designed, which were elaborated either by condensation of a lithium salt of 3-(N,N-dibenzyl)aminopropionic acid methyl ester with ethyl benzoformate or by Baylis-Hillman reaction of ethyl acrylate with ethyl benzoformate and sub...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200600182
更新日期:2007-02-01 00:00:00
abstract::Cardiotoxicity is a common side effect of a large variety of drugs that is often caused by off-target human ether-à-go-go-related gene (hERG) potassium channel blockade. In this study, we designed and synthesized a series of derivatives of the class III antiarrhythmic agent E-4031. These compounds where evaluated in a...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100366
更新日期:2012-01-02 00:00:00
abstract::Iron is essential for the pathogenicity and virulence of Mycobacterium tuberculosis, which synthesises salicyl-capped siderophores (mycobactins) to acquire this element from the host. MbtA is the adenylating enzyme that catalyses the initial reaction of mycobactin biosynthesis and is solely expressed by mycobacteria. ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900217
更新日期:2019-10-04 00:00:00
abstract::Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor 1 (TGR5) is considered a potential target for the treatment of type 2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300144
更新日期:2013-07-01 00:00:00
abstract::The less polar π-surface of protein amide groups is exposed in many receptor binding sites, either as part of the backbone or in Gln/Asn side chains. Using quantum chemical calculations and Protein Data Bank (PDB) searches on model systems, we investigate the energetics and geometric preferences for the stacking on am...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200512
更新日期:2013-03-01 00:00:00
abstract::Detailed information on the metabolic fate of lead compounds can be a powerful tool for an informed approach to the stabilization of metabolically labile compounds in the lead optimization phase. The combination of high performance liquid chromatography (HPLC) with nuclear magnetic resonance (NMR) spectroscopy and mas...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700203
更新日期:2008-01-01 00:00:00
abstract::The therapeutic potential of photoactive CO-releasing molecules (photoCORMs) have called for close examination of the roles of the ligand(s) and the central metal atoms on the overall photochemical labilization of the metal-CO bonds. Along this line, we have synthesized four metal complexes, namely, [MnBr(azpy)(CO)3 ]...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402007
更新日期:2014-06-01 00:00:00
abstract::The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recen...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402278
更新日期:2014-12-01 00:00:00
abstract::We report the synthesis of trifluoromethylated metallocenes (M=Fe, Ru) and related metal-free compounds for comparison of their biological properties with the aim to establish structure-activity relationships toward the anti-proliferative activity of this compound class. All new compounds were comprehensively characte...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402001
更新日期:2014-06-01 00:00:00
abstract::Drugs may have polypharmacological phenomena, that is, in addition to the desired target, they may also bind to many undesired or unknown physiological targets. As a result, they often exert side effects. In some cases, off-target interactions may lead to drug repositioning or to explaining a drug's mode of action. He...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500123
更新日期:2015-07-01 00:00:00
abstract::β-Lactamases (BLs) are important antibiotic-resistance determinants that significantly compromise the efficacy of valuable β-lactam antibacterial drugs. Thus, combinations with BL inhibitor were developed. Avibactam is the first non-β-lactam BL inhibitor introduced into clinical practice. Ceftazidime-avibactam represe...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800213
更新日期:2018-07-18 00:00:00
abstract::Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure and facilitates the localisation of transcriptional complexes to specific genes, thereby regulating epigenetically controlled processes including ge...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300259
更新日期:2014-03-01 00:00:00
abstract::Protein-protein and protein-carbohydrate interactions as a means to target the cell surface for therapeutic applications have been extensively investigated. However, carbohydrate-carbohydrate interactions (CCIs) have largely been overlooked. Here, we investigate the concept of CCI-mediated drug delivery. Lactose-funct...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500046
更新日期:2015-05-01 00:00:00
abstract::A small set of aggrecanase inhibitors based on the pyrrolo[3,4-c]quinolin-1-one or oxoisoindoline frameworks bearing a 4-(benzyloxy)phenyl substituent and different zinc binding groups were rationally designed and evaluated in silico by docking studies using the crystal structure of the ADAMTS-5 catalytic domain (PDB ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200900523
更新日期:2010-05-03 00:00:00
abstract::Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800487
更新日期:2018-11-06 00:00:00
abstract::Peroxisome proliferator-activated receptors (PPARs) have been studied extensively over the last few decades and have been assessed as molecular targets for the development of drugs against metabolic disorders. A rapid increase in understanding of the physiology and pharmacology of these receptors has occurred, togethe...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201300250
更新日期:2013-10-01 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::Digital Drug Discovery: Guest Editors Andreas Bender (University of Cambridge) and Nathan Brown (BenevolentAI) present the 20 articles included in this Special Issue on Cheminformatics in Drug Design. As they summarize each article, they also discuss the common themes within in silico drug discovery that these papers ...
journal_title:ChemMedChem
pub_type: 社论
doi:10.1002/cmdc.201800123
更新日期:2018-03-20 00:00:00
abstract::The enzyme cyclooxygenase-2 (COX-2) is overexpressed in many cancers, cardiovascular disease, neurodegenerative disorders, and arthritis. Selective inhibitors of COX-2 have been developed as therapeutics or preventive agents for these diseases. However, recent reports have revealed a significant increase in cardiovasc...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200500032
更新日期:2006-06-01 00:00:00
abstract::A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000346
更新日期:2010-11-08 00:00:00
abstract::Three photoswitchable tetrapeptides, based on a known synthetic antibacterial, were designed and synthesized to determine activity against Staphylococcus aureus. Each peptide contains an azobenzene photoswitch incorporated into either the N-terminal side chain (1), C-terminal side chain (2), or the C-terminus (3) to a...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000280
更新日期:2020-08-19 00:00:00
abstract::First reported in the late 1930s and partly explained in 1970, the antibacterial activity of pectin remained almost ignored until the late 1990s. The concomitant emergence of research on natural antibacterials and new usages of pectin polysaccharides, including those in medicine widely researched in Russia, has led to...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000518
更新日期:2020-08-28 00:00:00
abstract::Loperamide (1a), an opioid receptor agonist, is in clinical use as an antidiarrheal agent. Carbon/silicon exchange (sila-substitution) at the 4-position of the piperidine ring of 1a (R3 COH→R3 SiOH) leads to sila-loperamide (1b). Sila-loperamide was synthesized in a multistep procedure, starting from triethoxyvinylsil...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500040
更新日期:2015-05-01 00:00:00
abstract::Modern organizations conducting drug-discovery programs frequently apply high-throughput screening to generate novel hit structures for the indications of interest. Systematic hit-to-lead processes have been established at most pharmaceutical companies to ensure a smooth conversion of hits into high-quality lead struc...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200500031
更新日期:2006-01-01 00:00:00
abstract::In an attempt to develop potent anticancer agents, a series of 2-anilinonicotinyl-linked acrylamide conjugates were designed, synthesized, and evaluated for cytotoxic activity against various human cancer cell lines, anti-tubulin activity and cell-cycle effects. Among the series, compounds 6 d [(E)-N-(6-fluorobenzo[d]...
journal_title:ChemMedChem
pub_type: 杂志文章,收录出版
doi:10.1002/cmdc.201400036
更新日期:2014-03-28 00:00:00
abstract::The consumption of Brassica vegetables provides beneficial effects through organic isothiocyanates (ITCs), products of the enzymatic hydrolysis of glucosinolate secondary metabolites. The ITC l-sulforaphane (l-SFN) is the principle agent in broccoli that demonstrates several modes of anticancer action. While the antic...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800348
更新日期:2018-08-20 00:00:00