Abstract：
:Activity-based probes (ABPs) have found increasing use in functional proteomics studies. Recently, ABPs that can be employed in combination with click chemistry gained particular attention due to their flexible application in vitro and in vivo. Moreover, there is a continuous need for new ABPs that target small subsets of enzymes. We here report novel clickable ABPs based on the 4-chloro-isocoumarin (IC) electrophile, a mechanism-based inhibitor scaffold that covalently binds serine proteases. We describe the synthesis of a small library of IC ABPs containing an alkyne function and a set of diverse selectivity elements. The different substituents on the IC structure determine which proteases are bound, showing good correlation with the preferred substrate preferences. The IC ABPs can detect their target proteases in a proteome background in a sensitive manner (down to 0.007% of total protein). Furthermore, we show activity-dependent and selective labeling of endogenous proteases in a tissue proteome. These ICs therefore represent a valuable extension to already existing ABPs for serine proteases and may be instrumental in future elucidation of serine protease functions.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Haedke U,Götz M,Baer P,Verhelst SHdoi
10.1016/j.bmc.2011.03.014subject
Has Abstractpub_date
2012-01-15 00:00:00pages
633-40issue
2eissn
0968-0896issn
1464-3391pii
S0968-0896(11)00195-7journal_volume
20pub_type
杂志文章abstract：:Molecular combinations of two antioxidants (i.e., ascorbic acid and the pharmacophore of alpha-tocopherol), namely the 2,3-dihydroxy-2,3-enono-1,4-lactone and the chromane residues, have been designed and tested for their radical scavenging activities. When evaluated for their capability to inhibit malondialdehyde (MD...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)00205-4
更新日期：2000-12-01 00:00:00
abstract：:The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellul...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.01.020
更新日期：2017-06-01 00:00:00
abstract：:The conformational profiles of a selected group of a new series of small linear and cyclic penta- and hexapeptides, inspired on the C-terminal segment of second-generation bradykinin (BK) antagonists, were independently computed in order to assess the chemical and geometrical requirements necessary for BK antagonism. ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00084-4
更新日期：1998-09-01 00:00:00
abstract：:Synthesis of two novel 6-s-cis analogues of 1alpha,25-dihydroxyvitamin D3 are described using shikimic acid and its 4-epi isomer as versatile chiral starting materials. These derivatives contain a 2beta-(3'-hydroxypropoxy) moiety or a 2beta,3beta-epoxy group into 1alpha,25-OH(2)-19-nor-pre-D3. The synthesized analogue...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.10.053
更新日期：2008-12-15 00:00:00
abstract：:A novel series of mutilin 14-carbamates has been discovered as a result of structure-activity studies on the naturally occurring antibiotic pleuromutilin (1). In particular, the 4-methoxybenzoylcarbamate, SB-222734 (15o) displays potent antibacterial activity against a number of bacterial pathogens which are resistant...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)00338-2
更新日期：2001-05-01 00:00:00
abstract：:Quaternary carbolinium salts have been reported to show improved antimalarial activity and reduced cytotoxicity as compared to electronically neutral beta-carbolines. In this study, mono- and di-methylated quaternary carbolinium cations of manzamine A were synthesized and evaluated for their in vitro antimalarial and ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.05.079
更新日期：2008-07-15 00:00:00
abstract：:We complement new physically interpretable descriptors inspired by the Lipinski's rules of drug bioavailability with others obtained from the Dragon 3.0 software, in order to find the best QSPR relationship for aqueous solubilities of 100 structurally heterogeneous organic, drug-like compounds. The simultaneous linear...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.03.044
更新日期：2007-06-01 00:00:00
abstract：:The pyrimido[1,2-a][1,4]benzodiazepines (1a-c) and the 8-membered analogues (diazocines 2a and 2b) were separated into their atropisomers with HPLC on a chiral column. High stereochemical stability was observed in the atropisomer of the 8-membered derivatives (2a and 2b), and the 1,4-benzodiazepine (1c) with 2'-chloro...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.09.037
更新日期：2008-11-01 00:00:00
abstract：:Four stereoisomers of roseoside (vomifoliol glucosides) were synthesized using glucose as a chiral resolving reagent. The four synthetic stereoisomers exhibited inhibitory activity on leukotriene release from mouse bone marrow-derived cultured mast cells (BMCMC). The (6S)-isomers of roseoside were about twice as activ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.11.002
更新日期：2009-01-01 00:00:00
abstract：:Influenza is a continuing world-wide public health problem that causes significant morbidity and mortality during seasonal epidemics and sporadic pandemics. The purpose of the study was synthesis and investigation of antiviral activity of camphor-based symmetric diimines and diamines. A set of C2-symmetric nitrogen-co...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2014.02.038
更新日期：2014-04-01 00:00:00
abstract：:Two types of structural variants of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] were prepared by a chemoenzymatic route. These 6-O-substituted analogues retained the biological activity of Ins(1,4,5)P3, and were able to elicit Ca2+ release from porcine brain microsomes. Moreover, these derivatives allowed the pr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)82196-3
更新日期：1994-01-01 00:00:00
abstract：:Hypertension is a diverse illness interlinked with cerebral, cardiovascular (CVS) and renal abnormalities. Presently, the malady is being treated by focusing on Renin- angiotensin system (RAS), voltage-gated calcium channels, peripheral vasodilators, renal and sympathetic nervous systems. Cardiovascular and renal abno...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2020.115466
更新日期：2020-05-15 00:00:00
abstract：:Chemical inhibition of proteins involved in chromatin-mediated signaling is an emerging strategy to control chromatin compaction with the aim to reprogram expression networks to alter disease states. Protein methyltransferases constitute one of the protein families that participate in epigenetic control of gene expres...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.01.049
更新日期：2013-04-01 00:00:00
abstract：:Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an integral part of the currently available combination antiretroviral therapy (cART) contributing to reduce the AIDS-mortality and turned the disease from lethal to chronic. In this context we recently reported a series of 6-chloro-1-(3-methylphenylsu...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.05.040
更新日期：2017-07-15 00:00:00
abstract：:The following study describes the synthesis of new benzanilide derivatives and their pharmacological investigation on smooth muscle preparations of guinea pigs. All compounds were synthesized in good yields and showed a spasmolytic activity without significant effect on vascular smooth muscles and heart muscle prepara...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.04.057
更新日期：2008-06-01 00:00:00
abstract：:Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and regulates the expression of target genes through ligand binding. To express the target gene, coactivator binding to the VDR/ligand complex is essential. Although there are many coactivators in living cells, precise interactions between coacti...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.11.020
更新日期：2017-01-15 00:00:00
abstract：:Beta-carboline-benzoquinolizidine plant alkaloid deoxytubulosine (DTB) was evaluated and assessed for the first time for its biochemical and biological activity employing the biomarker dihydrofolate reductase (DHFR) (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) as the probe enzyme, a key target in cance...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00262-4
更新日期：1999-06-01 00:00:00
abstract：:Based on 2-(4-phenoxybenzoyl)-5-hydroxyindole (2), a novel structural class of CaMKII inhibitors were synthesized and further optimized. The strong acidity of the hydroxyl group and the lipophilic group at the 4 and 6-positions were found to be necessary for strong CaMKII inhibition. Compound 25 was identified as a pr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.09.048
更新日期：2012-12-01 00:00:00
abstract：:We have developed esonarimod, (+/-)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the preparation of the enantiomers of (+/-)-deacetylesonarimod, the pharmaceutically active metabolites of esonarimod, and comparison of their antirheumatic activities. No s...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(02)00084-6
更新日期：2002-08-01 00:00:00
abstract：:Thiazolyl peptides are a class of thiazole-rich macrocyclic potent antibacterial agents. Recently, we described thiazomycin, a new member of thiazolyl peptides, discovered by a thiazolyl peptide specific chemical screening. This method also allowed for the discovery of a new thiazolyl peptide, thiazomycin A, which car...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.08.079
更新日期：2008-10-01 00:00:00
abstract：:4-Oxalocrotonate tautomerase (4-OT) catalyzes the isomerization of 4-oxalocrotonate, 1, to 2-oxo-3E-hexenedioate, 3, using a general acid/base mechanism that involves a conserved N-terminal proline residue. The P1A and P1G mutants have been shown to catalyze this isomerization but at reduced rates. Analysis of these m...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(02)00385-1
更新日期：2002-12-01 00:00:00
abstract：:Pin1 (Protein interacting with NIMA1) is a peptidyl prolyl cis-trans isomerase (PPIase) which specifically catalyze the conformational conversion of the amide bond of pSer/Thr-Pro motifs in its substrate proteins and is a novel promising anticancer target. A series of new thiazole derivatives were designed and synthes...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.09.049
更新日期：2016-11-15 00:00:00
abstract：:A library of 25-membered chalcones was prepared by parallel synthesis. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Several chalcones showed in vitro antiparasitic activity against Giardia lamblia. The highest activity observed for the IC(50) v...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.02.052
更新日期：2009-09-15 00:00:00
abstract：:The alpha-FR has been reported to be overexpressed in many carcinomas, in particular those of the ovary and uterus. The high expression of alpha-FR in some tumours compared with normal tissues has been exploited over the last decade for folate-mediated targeting of macromolecules, anticancer drugs, imaging agents and ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.03.001
更新日期：2006-07-15 00:00:00
abstract：:The okadaic acid class of naturally occurring toxins is a structurally diverse group of molecules that inhibit the protein phosphatases PP1 and PP2A. Studies providing information about the mode of binding between the toxins and the phosphatases contribute to an overall understanding of the signal transduction pathway...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/s0968-0896(97)00146-6
更新日期：1997-09-01 00:00:00
abstract：:3- And 4-imidazol-1-yl-methyl substituted biphenyl compounds (named as meta- and para-substituted compounds) were synthesized bearing additional substituents in 3'-/4'-position as inhibitors of P450 17 (17alpha-hydroxylase-C17,20-lyase). P450 17 is the key enzyme of androgen biosynthesis. Its inhibition is a novel the...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(99)00160-1
更新日期：1999-09-01 00:00:00
abstract：:Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 an...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.03.009
更新日期：2007-06-01 00:00:00
abstract：:EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.06.005
更新日期：2017-08-01 00:00:00
abstract：:A system for identification of bioisosteric scaffolds is presented. The system uses a database of over 7000 scaffolds extracted from bioactive molecules. Scaffolds in the database are characterized by their size, shape, pharmacophore features and several ADME descriptors. Also properties characterizing electron-donati...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.02.058
更新日期：2012-09-15 00:00:00
abstract：:The design, synthesis, and biological evaluation of a series of pyrrole and pyrazole congeners 2 of suramin, directed toward the development and identification of new ligands that complex the human fibroblast growth factor (bFGF), thereby inhibiting tumor-promoted angiogenesis, is reported. Compounds 2 were evaluated ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00052-2
更新日期：1998-07-01 00:00:00
