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 identify an efficient single-chain probe that can quantify RA with significant sensitivity. The optimal probe consisted of four components: the N- and C-terminal fragments of artificial luciferase variant-16 (ALuc16), the ligand binding domain of retinoic acid receptor α (RARα LBD), and an LXXLL interaction motif. This probe showed a 5.2-fold greater bioluminescence intensity in response to RA when compared to the vehicle control in live mammalian cells. The probe was highly selective to all-trans-RA (at-RA), and highly sensitive in determining at-RA levels in cells derived from tumor xenografts created using MDA-MB-231 cells engineered to stably express the probe. We also detected RA levels in serum and cerebrospinal fluid. Using this probe, the detection limit for at-RA was ∼10-9.5 M, with a linear range of two orders. We present a highly useful technique to quantitatively image endogenous at-RA levels in live mammalian cells expressing novel single-chain bioluminescence probes.
journal_name
ACS Comb Scijournal_title
ACS combinatorial scienceauthors
Kim SB,Fujii R,Nishihara R,Bose RJ,Citterio D,Suzuki K,Massoud TF,Paulmurugan Rdoi
10.1021/acscombsci.9b00035subject
Has Abstractpub_date
2019-06-10 00:00:00pages
473-481issue
6eissn
2156-8952issn
2156-8944journal_volume
21pub_type
杂志文章abstract：:We have achieved an efficient solution-phase parallel synthesis of a library of natural piper-amide-like compounds from the bifunctional β-phosphono-N-hydroxy-succinimidyl ester intermediate. The primary important feature in our study is the construction of natural-product-like molecules through the adaptation of soph...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co400003d
更新日期：2013-04-08 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：:A combinatorial library having 66 different ternary compositions of Pd-Ir-Ce was prepared via the impregnation method to find the optimum ternary composition with the highest performance toward oxygen reduction reaction (ORR) in acid media. Its performance in ORR activity of the combinatorial array was evaluated throu...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co400008v
更新日期：2013-11-11 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：: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
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：:A series of LiMn1-x-yFexVyPO4 (LMFVP) nanomaterials have been synthesized using a pilot-scale continuous hydrothermal synthesis process (CHFS) and evaluated as high voltage cathodes in Li-ion batteries at a production rate of 0.25 kg h-1. The rapid synthesis and screening approach has allowed the specific capacity of ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00035
更新日期：2016-11-14 00:00:00
abstract：:A potentiometric Pb(II)-selective sensor was fabricated by a combinatorial screening of electrically conducting polysulfoaminoanthraquinone (PSA) nanoparticles as a solid ionophore, ion exchangers (oleic acid (OA) and NaTPB), plasticizers in a polyvinyl chloride (PVC) matrix, membrane thickness, inner filling ion spec...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co400140g
更新日期：2014-03-10 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：: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：:A high throughput combinatorial synthesis utilizing inkjet printing of precursor inks was used to rapidly evaluate Bi-alloying into double perovskite oxides for enhanced visible light absorption. The fast visual screening of photo image scans of the library plates identifies 4-metal oxide compositions displaying an in...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00177
更新日期：2020-12-14 00:00:00
abstract：:Disulfide exchange screening is a method for evaluating the binding of small molecule fragments to proteins that have at least one accessible cysteine. While operationally simple, it does require a large library of small fragment molecules bearing disulfide-containing side chains. These specialized fragments are not a...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co200038g
更新日期：2011-05-09 00:00:00
abstract：:Preparative RP-LCMS is widely used to purify compounds from crude reaction mixtures in drug discovery today. Method development for preparative Liquid Chromatography-Mass Spectrometry (LCMS) consists of finding the right balance between speed and quality, often leading to the use of fast generic gradients (5-95% organ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co200197b
更新日期：2012-04-09 00:00:00
abstract：:An expedient and metal-free synthetic protocol for construction of substituted quinolines has been developed from anilines and phenylacetaldehydes using imidazolium cation-based ionic liquids as the reaction medium. Mechanistic analysis indicated that the reaction occurs through C-C and C-N bond formation to produce i...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500047w
更新日期：2014-11-10 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：:Cr-Al-N thin film materials libraries were synthesized by combinatorial reactive high power impulse magnetron sputtering (HiPIMS). Different HiPIMS repetition frequencies and peak power densities were applied altering the ion to growth flux ratio. Moreover, time-resolved ion energy distribution functions were measured...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00123
更新日期：2019-12-09 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：: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：: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：: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：:Magnetization using cheap and minimally toxic materials, such as iron oxide nanoparticles can enable easy separation of cells from culture medium and is relevant to several industrial applications. Here, we show that cell surface expression of a mutant protein that binds iron oxide can enable efficient magnetization o...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.8b00084
更新日期：2018-10-08 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：:An efficient and straightforward synthetic protocol has been developed for the diversity-oriented synthesis of highly functionalized piperidines containing a Meldrum's acid moiety via pseudo five-component reaction between aromatic aldehydes, ammonium acetate, substituted β-nitrostyrenes and Meldrum's acid for the gen...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co4001502
更新日期：2014-03-10 00:00:00
abstract：:Solid-phase synthetic strategies toward the generation of libraries of biologically relevant molecules were developed using olefin cross-metathesis as a key step. It is remarkably the formal alkane metathesis based on a one-pot, microwave-assisted, ruthenium-catalyzed cross-metathesis and reduction to obtain Csp3-Csp3...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500176b
更新日期：2015-02-09 00:00:00
abstract：:Ultrasound-assisted synthesis of benzimidazo[2,1-b]quinazolin-1(1H)-ones was achieved via piperidine-catalyzed three-component reaction of 2-aminobenzimidazoles, an aromatic aldehyde, and 1,3-dione in aqueous isopropanol. This mechanism was first suspected following our identification of unusual reaction intermediates...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00186
更新日期：2016-03-14 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：:Electromanipulation and electrical characterization of cancerous cells is becoming a topic of high interest as the results reported to date demonstrate a good differentiation among various types of cells from an electrical viewpoint. Dielectrophoresis and broadband dielectric spectroscopy are complementary tools for s...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00109
更新日期：2020-11-09 00:00:00
abstract：:A Fe-Co-Nb thin film materials library was deposited by combinatorial magnetron sputtering and investigated by high-throughput methods to identify new noncubic ferromagnetic phases, indicating that combinatorial experimentation is an efficient method to discover new ferromagnetic phases adequate for permanent magnet a...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00116
更新日期：2015-11-09 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：:A combination of MACOS scale-out and ROMP-derived oligomeric triazole phosphates (OTP(n)) have been successfully utilized for the preparation of a 106-member library of triazole containing benzothiaoxazepine-1,1-dioxides. This report demonstrates the utilization of a suite of soluble OTP(n) reagents for facile (triazo...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co2001839
更新日期：2012-04-09 00:00:00
