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 benefit from high target expression, robustly adherent mammalian cells, and nanomolar affinity ligands. This study evaluates a modified format with mammalian cells immobilized to magnetic beads; yeast-displayed fibronectin domain and affibody ligands of known affinities and cells with expression ranges of epidermal growth factor receptor (EGFR) and CD276 elucidate important parameters to ligand enrichment and yield in cell suspension panning with comparison to adherent panning. Cell suspension panning is hindered by significant background of nondisplaying yeast but exhibits yield advantages in model EGFR systems for a high affinity (KD = 2 nM) binder on cells with both high (106 per cell) target expression (9.6 ± 0.6% vs 3.2 ± 0.4%, p < 0.0001) and mid (105) target expression (2.3 ± 0.5% vs 0.41 ± 0.09%, p = 0.0008), as well as for a low affinity (KD > 600 nM) binder on high target expression cells (2.0 ± 0.5% vs 0.017 ± 0.005%; p = 0.001). Significant enrichment was observed for all EGFR systems except the low-affinity, high expression system. The CD276 system failed to provide significant enrichment, indicating that this technique may not be suitable for all targets. Collectively, this study highlights new approaches that yield successful enrichment of yeast-displayed ligands via panning on immobilized mammalian cells.
journal_name
ACS Comb Scijournal_title
ACS combinatorial scienceauthors
Lown PS,Hackel BJdoi
10.1021/acscombsci.0c00036subject
Has Abstractpub_date
2020-05-11 00:00:00pages
274-284issue
5eissn
2156-8952issn
2156-8944journal_volume
22pub_type
杂志文章abstract：:Polymer-supported N-(2-oxo-ethyl)-derivatized Ser/Thr/Cys-containing dipeptides were synthesized and subjected to acid-mediated tandem N-acylium ion cyclization-nucleophilic addition to yield tetrahydro-2H-oxazolo[3,2-a]pyrazin-5(3H)-ones. The reaction conditions and building-block combinations for stereoselective syn...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co3001567
更新日期：2013-03-11 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：:This study investigates perovskite hydrides (ABH3) comprising alkali metals of A, where A is Li, Na, K, Rb, or Cs, and alkaline-earth metals of B, where B is Be, Mg, Ca, Sr, or Ba, to screen the highest potential hydrides for hydrogen release. Herein, we investigated the most favorable dehydrogenation pathway for each...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00108
更新日期：2019-11-11 00:00:00
abstract：:Optical bandgap mapping of Nb-Ti mixed oxides anodically grown on a thin film parent metallic combinatorial library was performed via variable angle spectroscopic ellipsometry (VASE). A wide Nb-Ti compositional spread ranging from Nb-90 at.% Ti to Nb-15 at.% Ti deposited by cosputtering was used for this purpose. The ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00162
更新日期：2017-02-13 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：:In this article, an original one-pot method is utilized to synthesize a variety of derivatives of naphtho[2,1-b]furan-2(1H)-one via a pseudo-four-component domino reaction of aryl aldehydes, acetic anhydride, hippuric acids, and 2-naphthols catalyzed by HSW@SPIONs. This reaction illustrates an array of attractive feat...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00018
更新日期：2015-08-10 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：:A combination of flow and batch chemistries has been successfully applied to the assembly of a series of trisubstituted drug-like pyrrolidines. This study demonstrates the efficient preparation of a focused library of these pharmaceutically important structures using microreactor technologies, as well as classical par...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co2000357
更新日期：2011-07-11 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：:Parallel solution-phase synthesis of combinatorial libraries of dihydroindenoisoquinolines employing a sequential Cu(I)/Pd(0)-catalyzed multicomponent coupling and annulation protocol was realized. The scope and limitations of the protocol with respect to the substitution pattern in the aryl ring of the indene core, a...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co200027c
更新日期：2011-09-12 00:00:00
abstract：:Thirteen 5-hetarylaminopyrazoles were synthesized in 62-93% yield through the arylation of 1-isopropyl- and 1-phenyl-5-aminopyrazoles with electrophilic hetarylhalides under optimized conditions. Condensation of 5-hetarylaminopyrazoles with carbonyl compounds facilitated by AcOH or Me(3)SiCl furnished 23 pyrazolo[3,4-...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co300063x
更新日期：2012-08-13 00:00:00
abstract：:DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distributio...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00192
更新日期：2017-03-13 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：: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：:Combinatorial synthesis of Li-ion batteries has proven extremely powerful in screening complex compositional spaces for next-generation materials. To date, no Na-ion counterpart exists wherein Na-ion cathodes can be synthesized in such a way to be comparable to that obtained in bulk synthesis. Herein, we develop a syn...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00181
更新日期：2020-06-08 00:00:00
abstract：:A sequential single-flask multicomponent reactions is highly effective for the synthesis of 1,2-dihydroisoquinolines through amidealkylation from intermediate N-acylisoquinolinium salts under mild conditions. N-Acylisoquinolinium ions and trichloromethyl-1-(1H-indol-3-yl)isoquinoline-2(1H)-carboxylate have demonstrate...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00001
更新日期：2015-08-10 00:00:00
abstract：:We report the first example of venting-while-heating microwave-assisted synthesis of a small library of 3-arylthioindoles. Compounds were prepared in excellent isolated yields (90-98%) within 4 min in a closed vessel by treating indoles with disulfides in the presence of sodium hydride in anhydrous N,N-dimethylformami...
journal_title：ACS combinatorial science
pub_type： 信件
doi：10.1021/co200165j
更新日期：2012-04-09 00:00:00
abstract：:A one-pot, three-component synthesis of benzimidazole-linked thiazolidines from 2-cyanomethyl benzimidazole, iso-, isothio-, or isoselenocyanates and 1,2-dichloroethane is reported. Isolation of the key intermediate formed during the course of the reaction validates its mechanistic pathway. Under the same reaction con...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00161
更新日期：2020-01-13 00:00:00
abstract：:Acetylenic tertiary alcohols are well-known to be compounds that are biologically more stable than their corresponding secondary alcohols. The linkage of an acetylenic compound to a polymer support and further introduction of molecular diversity was found to be an interesting way to generate libraries of hydroxy acety...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co300034y
更新日期：2012-06-11 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：:The thin film system Ti-Ni-Si was investigated using methods of combinatorial materials science. A thin film composition spread library of the system was fabricated using combinatorial magnetron sputtering. The functional properties Seebeck coefficient, electrical resistivity, and luminance were determined using high-...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.8b00181
更新日期：2019-05-13 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
abstract：:Fourteen (hetero-)(arylidene)arylhydrazide derivatives (ABH1-ABH14) were synthesized, and their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE) were evaluated. Compound ABH5 most potently inhibited MAO-B with an IC50 value of 0.025 ± 0.0019 μM; ABH2 and ABH3 exhibited high IC50 ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00136
更新日期：2020-11-09 00:00:00
abstract：:Thin films of two types of high-entropy oxides (HEOs) have been deposited on 76.2 mm Si wafers using combinatorial sputter deposition. In one type of the oxides, (MgZnMnCoNi)O x , all the metals have a stable divalent oxidation state and similar cationic radii. In the second...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00159
更新日期：2020-12-14 00:00:00
abstract：:A sequential one-pot, two-step, three-component reaction for efficient synthesis of spiro-substituted 1,3-thiazine library has been developed. The syntheses were achieved by reacting cyanoacetamide with isothiocyanate derivatives to give rise to 2-cyano-3-mercaptoacrylamides, which are trapped in situ by various cyclo...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co100034v
更新日期：2011-01-10 00:00:00
abstract：:A new one-pot, three component reaction involving the use of Julia reagent, aldehyde, and sodium azide was developed for the efficient synthesis of N-unsubstituted 1,2,3-triazoles. This reaction could be carried out under mild reaction conditions without any precaution, and broad scope of substrates, both respect to J...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co5001597
更新日期：2015-03-09 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：: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：:Copolymerization of isoprene (IP) with glycidyl methacrylate (GMA) was performed under RAFT (reversible addition-fragmentation chain-transfer) polymerization conditions in a platform for high-output experimentation. Covering the range between 1 and 0.2 molar fraction of IP in the feed, four sets of reactions were carr...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00110
更新日期：2019-12-09 00:00:00
abstract：:The reactions of vinyl malononitriles with 3-phenacylideneoxindoles in ethanol in the presence of DBU as base resulted in the functionalized spirocyclic oxindoles through the domino Michael addition and intramolecular nucleophilic addition to cyano group. On the other hand, the similar reaction in the presence of pipe...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500006c
更新日期：2014-06-09 00:00:00
