Abstract：
:On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double point-mutated version of the human FKBP12 protein, known as the destabilizing domain (DD). Inspired by the decoded library hits, unnatural peptide structures were screened in a novel on-bead assay, which was useful for a rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure refinement was accomplished using small quantities of library building blocks.
journal_name
ACS Comb Scijournal_title
ACS combinatorial scienceauthors
Madsen D,Jørgensen FP,Palmer D,Roux ME,Olsen JV,Bols M,Schoffelen S,Diness F,Meldal Mdoi
10.1021/acscombsci.9b00197subject
Has Abstractpub_date
2020-03-09 00:00:00pages
156-164issue
3eissn
2156-8952issn
2156-8944journal_volume
22pub_type
杂志文章abstract：:A novel method of evaluating the enantioselectivity of chiral receptors is investigated. It involves extraction of an ionic guest in racemic form from an ion-exchange resin to the organic solvent, where it is bound by a chiral receptor. The enantioselectivity of the examined receptor is determined simply by measuring ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00075
更新日期：2015-09-14 00:00:00
abstract：:A one-bead one-compound (OBOC) library of peptide-based imaging agents was developed where a 19F-containing moiety was added onto the N-terminus of octamer peptides through copper-free click chemistry prior to screening of the library. This created a library of complete imaging agents that was screened against CXCR4, ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00146
更新日期：2020-03-09 00:00:00
abstract：:Retinoic acid (RA) is a key metabolite necessary for embryonic development and differentiation in vertebrates. We demonstrate the utility of genetically encoded, ligand-activatable single-chain bioluminescence probes for detecting RAs from different biological sources. We examined 13 different molecular designs to ide...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00035
更新日期：2019-06-10 00:00:00
abstract：:A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that interacts with TcBDF3 with affinity in the submicromolar range and that shows interes...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.7b00172
更新日期：2018-04-09 00:00:00
abstract：:Adleman's illustration of molecular computing using DNA paved the way toward an entirely new direction of computing (Adleman, L. M. Science 1994, 266, 1021). The exponential time complex combinatorial problem on a traditional computer turns out to be a separation problem involving a polynomial number of steps in DNA c...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00150
更新日期：2020-05-11 00:00:00
abstract：:The exploration of new alloys with desirable properties has been a long-standing challenge in materials science because of the complex relationship between composition and microstructure. In this Research Article, we demonstrate a combinatorial strategy for the exploration of composition dependence of microstructure. ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00040
更新日期：2016-10-10 00:00:00
abstract：:Functionalized chromenes have been synthesized via highly selective metal-free domino reactions from ketones and phenols. 2H-Chromenes, 4H-chromenes, spiran and benzocyclopentane can be respectively prepared starting from the corresponding cyclic ketones, aryl methyl ketones, acetone, and 3-pentanone. ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co3000506
更新日期：2012-08-13 00:00:00
abstract：:We propose to minimize the sampling time for high-throughput measurements of powder X-ray diffraction (XRD) and X-ray absorption fine structure (XAFS) in synchrotron radiation. The conventional synchrotron radiation powder X-ray diffraction method requires filling of a capillary tube, but a structure-refining diffract...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00174
更新日期：2020-12-14 00:00:00
abstract：:High-throughput experimentation provides efficient mapping of composition-property relationships, and its implementation for the discovery of optical materials enables advancements in solar energy and other technologies. In a high throughput pipeline, automated data processing algorithms are often required to match ex...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00053
更新日期：2016-11-14 00:00:00
abstract：:A build/couple/pair strategy for the synthesis of complex and densely functionalized small molecules is presented. The strategy relies on synthetically tractable building blocks (build), that is, diversely substituted hydrazides, α-hydroxy aldehydes, and boronic acids, which undergo Petasis 3-component reactions (coup...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500091f
更新日期：2015-01-12 00:00:00
abstract：:In this research, MgAl-CO32- nanolayered double hydroxide (NLDH) was synthesized through a facile coprecipitation method, followed by a hydrothermal treatment. The prepared NLDHs were used as a hydrophilic nanofiller for improving the performance of the PVDF-based ultrafiltration membranes. The main objective of this ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.7b00046
更新日期：2017-07-10 00:00:00
abstract：:A novel parallel medicinal chemistry (PMC)-enabled synthesis of 1H-pyrazolo[3,4-d]pyrimidines employing condensation of easily accessible N-pyrazolylamides and nitriles has been developed. The presented studies describe singleton and library enablements that allowed rapid generation of molecular diversity to examine C...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.7b00116
更新日期：2017-11-13 00:00:00
abstract：:The Au-Al alloy system was investigated via a combinatorial thin film sputtering method for its potential as a plasmonic material. Au xAl1- x combinatorial libraries were cosputtered from Au and Al elemental targets and the composition, phase, and dielectric function of a ∼350 nm film was determined using energy dispe...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.8b00091
更新日期：2018-11-12 00:00:00
abstract：:Applications of silica-ROMP reagents in a one-pot, sequential protocol have been developed for the synthesis of a variety of diverse benzoxathiazepine 1,1-dioxides. This protocol includes sulfonylation, intramolecular SNAr, alkylation with silica-supported oligomeric benzyl (Si-OBPn) and triazole (Si-OTPn) phosphates,...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00041
更新日期：2016-07-11 00:00:00
abstract：:A condition-based skeletal divergent synthesis was explored to achieve skeletal diversity in two component condensation reaction. Cyanomethyl benzimidazole was reacted with α-bromoketone under thermal conditions to furnish 2-aminofuranyl-benzimidazoles, while the same reaction afforded 3-cyano-benzopyrrolo-imidazoles ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.7b00052
更新日期：2017-07-10 00:00:00
abstract：:This work presents the first use of yeast-displayed protein targets for screening mRNA-display libraries of cyclic and linear peptides. The WW domains of Yes-Associated Protein 1 (WW-YAP) and mitochondrial import receptor subunit TOM22 were adopted as protein targets. Yeast cells displaying WW-YAP or TOM22 were magnet...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00171
更新日期：2020-12-14 00:00:00
abstract：:An efficient method is described for the solid-supported synthesis of imidazo[4,5-b]pyridines and imidazo[4,5-c]pyridines from 2,4-dichloro-3-nitropyridine. The key pyridine building block was reacted with polymer-supported amines, followed by replacement of the second chlorine with amines, nitro group reduction, and ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500090t
更新日期：2014-10-13 00:00:00
abstract：:An efficient discovery strategy by combining diversity-oriented synthesis and converging cellular screening is described. By a three-round screening process, we identified novel tricyclic pyrido[2,3-b][1,4]benzothiazepines showing potent inhibitory activity against paclitaxel-resistant cell line H460TaxR (EC50 < 1.0 μ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00010
更新日期：2016-05-09 00:00:00
abstract：:The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resyn...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00155
更新日期：2016-08-08 00:00:00
abstract：:Yeast surface display empowers selection of protein binding ligands, typically using recombinant soluble antigens. However, ectodomain fragments of transmembrane targets may fail to recapitulate their true, membrane-bound form. Direct selections against adhered mammalian cells empower enrichment of genuine binders yet...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00036
更新日期：2020-05-11 00:00:00
abstract：:Peptides are still difficult to synthesize when they contain sterically hindered amino acids, such as α,α-disubstituted amino acids and N-substituted amino acids. In this study, solid-phase syntheses of oligopeptides containing multiple α-aminoisobutyric acid (Aib) residues were performed in high yields by using a non...
journal_title：ACS combinatorial science
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doi：10.1021/acscombsci.7b00184
更新日期：2018-03-12 00:00:00
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journal_title：ACS combinatorial science
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doi：10.1021/co500006c
更新日期：2014-06-09 00:00:00
abstract：:A build/couple/pair (B/C/P) strategy was employed to generate a library of 7936 stereochemically diverse 12-membered macrolactams. All 8 stereoisomers of a common linear amine precursor were elaborated to form the corresponding 8 stereoisomers of two regioisomeric macrocyclic scaffolds via head-to-tail cyclization. Su...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co200161z
更新日期：2012-02-13 00:00:00
abstract：:This is a report on the early years of combinatorial materials science and technology. High-throughput technologies (HTTs) are found in life- and materials-science laboratories. Although HTTs have long been the standard in life sciences in academia as well as in industry, HTTs in materials science have become the stan...
journal_title：ACS combinatorial science
pub_type： 历史文章,杂志文章,评审
doi：10.1021/acscombsci.8b00189
更新日期：2019-06-10 00:00:00
abstract：:Metal-organic frameworks (MOFs) are nanoporous materials with exceptional host-guest properties poised for groundbreaking innovations in gas separation applications according to high-throughput (HT) screening data. However, MOF structural libraries are nearly infinite in practice and so statistical and information tec...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00188
更新日期：2016-05-09 00:00:00
abstract：:A one-pot parallel synthesis of N(1)-aryl-N(2)-alkyl-substituted oxamides with 2,2,2-trifluoroethyl chlorooxoacetate was developed. The synthesis of a library of 45 oxamides revealed higher efficiency of this reagent over the known ethyl chlorooxoacetate. The reagent was successfully used to prepare the known oxamide-...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00091
更新日期：2015-10-12 00:00:00
abstract：:A copper-catalyzed efficient one step three component strategy for preparing a library of aminoindolizino[8,7-b]indoles from N-substituted 1-formyl-9H-β-carbolines, secondary amines, and substituted alkynes with high atom economy has been developed. ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co300123y
更新日期：2012-12-10 00:00:00
abstract：:A microgradient-heater (MGH) was developed, and its feasibility as a tool for high-throughput materials science experimentation was tested. The MGH is derived from microhot plate (MHP) systems and allows combinatorial thermal processing on the micronano scale. The temperature gradient is adjustable by the substrate ma...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co3000488
更新日期：2012-10-08 00:00:00
abstract：:A novel three-component, two-step, one-pot nucleophilic aromatic substitution (SNAr)-intramolecular cyclization-Suzuki coupling reaction was developed for the synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synth...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.7b00119
更新日期：2017-12-11 00:00:00
abstract：:For a future structure-activity relationship (SAR) study, a library of desketoraloxifene analogues has been prepared by parallel synthesis using iodocyclization and subsequent palladium-catalyzed coupling reactions. Points of desketoraloxifene diversification involve the two phenolic hydroxyl groups and the aliphatic ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co200090p
更新日期：2011-09-12 00:00:00
