在新任主编 M.G. 的领导下，《组合化学杂志》以 ACS 组合科学的名义重新发行。斯克里普斯研究所的芬恩。该杂志的特点是扩大了范围，并将建立在组合化学杂志的遗产之上，该杂志是该领域被高度引用的领导者。

Under the leadership of the new editor M.G., the journal "ACS Combinatorial Science" has been relaunched. It is hosted by the Scripps Research Institute's Finn, featuring an expanded scope and building upon the legacy of the Combinatorial Chemistry Journal, which is a highly cited leader in the field.

在新任主编 M.G. 的领导下，《ACS Combinatorial Science》重新发行。该杂志由斯克里普斯研究所的芬恩主办，特色在于扩大了研究范围，并将建立在组合化学杂志的遗产之上，后者是该领域被高度引用的领导者。

ACS Combinatorial Science

Monosized beads of polar resins were synthesized for combinatorial chemistry and chemical biology by sustainable microchannel flow synthesis. Regular, biocompatible, and optically encoded beads could be efficiently prepared on large scale and in high yield. In a preparative flow polymerization instrument, taking advantage of a designed T-connector for droplet formation, quality beads were synthesized with accurate size control using a minimal amount of recirculating silicon oil as suspension medium. Bead-size was controlled through shear imposed by the silicon oil flow rate. This process provided 86% yield of ∼500 μm macrobeads beads within a 20 μm size range with no deformities or vacuoles, ideally suited for combinatorial chemistry and protein binding studies. The simple flow equipment consisted of a syringe pump for monomer and initiator delivery, a T-connector, a gear pump for oil recirculation, a long, heated coil of Teflon tubing and a collector syringe. The method was used for preparation of PEGA1900 beads, optically encoded with fluorescent microparticles. The microparticle matrix (MPM) encoded beads were tested in a MPM-decoder showing excellent recognition in bead decoding.

Hongxia Hu

Sergei Nikitin

Adam Bjørnholdt Berthelsen

Frederik Diness

Sanne Schoffelen

Morten Meldal

Sustainable Flow Synthesis of Encoded Beads for Combinatorial Chemistry and Chemical Biology

可持续流动合成编码微珠用于组合化学与化学生物学

We investigated the yield and distribution of macrocyclic products formed in combinatorial libraries (CLs) obtained via double-amidation reactions of methyl diesters with α,ω-diamines. The application of the static combinatorial chemistry (SCC) approach allowed us to generate a large number of macrocyclic diamides and tetraamides in single experiments. We show that high-pressure conditions accelerate the macrocyclization process but also have a great impact on the distribution of macrocyclic products in the presented libraries, promoting the formation of macrocyclic compounds and eliminating the linear ones. The distribution of macrocyclic products was also found to be strongly dependent on the structural features of the substrates employed. Furthermore, in three- and four-substrate CLs we observed the formation of a new type of hybrid tetraamides consisting of three different components.

Grzegorz Pikus

Agata Tyszka-Gumkowska

Janusz Jurczak

Static Combinatorial Chemistry: A High-Pressure Approach to the Synthesis of Macrocyclic Benzoamide Libraries

静态组合化学：一种高压合成大环苯甲酰胺库的方法

Peptide drug discovery has shown a resurgence since 2000, bringing 28 non-insulin therapeutics to the market compared to 56 since its first peptide drug, insulin, in 1923. While the main method of discovery has been biological display—phage, mRNA, and ribosome—the synthetic limitations of biological systems has restricted the depth of exploration of peptide chemical space. In contrast, DNA-encoded chemistry offers the synergy of large numbers and ribosome-independent synthetic flexibility for the fast and deeper exploration of the same space. Hence, as a bridge to building DNA-encoded chemical libraries (DECLs) of peptides, we have developed substrate-tolerant amide coupling reaction conditions for amino acid monomers, performed a coupling screen to illustrate such tolerance, developed protecting group strategies for relevant amino acids and reported the limitations thereof, developed a strategy for the coupling of α,α-disubstituted alkenyl amino acids relevant to all-hydrocarbon stapled peptide drug discovery, developed reaction conditions for the coupling of tripeptides likely to be used in DECL builds, and synthesized a fully deprotected DNA-decamer conjugate to illustrate the potency of the developed methodology for on-DNA peptide synthesis.

Olivier B. C. Monty

Nicholas Simmons

Srinivas Chamakuri

Martin M. Matzuk

Damian W. Young

Solution-Phase Fmoc-Based Peptide Synthesis for DNA-Encoded Chemical Libraries: Reaction Conditions, Protecting Group Strategies, and Pitfalls

基于Fmoc的溶液相肽合成用于DNA编码化学库：反应条件、保护基策略及陷阱

Therapies that bind with immune cells and redirect their cytotoxic activity toward diseased cells represent a promising and versatile approach to immunotherapy with applications in cancer, lupus, and other diseases; traditional methods for discovering these therapies, however, are often time-intensive and lack the throughput of related target-based discovery approaches. Inspired by the observation that the cytokine, IL-12, can enhance antileukemic activity of the clinically approved T cell redirecting therapy, blinatumomab, here we describe the structure and assembly of a chimeric immune cell-redirecting agent which redirects the lytic activity of primary human T cells toward leukemic B cells and simultaneously cotargets the delivery of T cell-stimulating IL-12. We further describe a novel method for the parallel assembly of compositionally diverse libraries of these bispecific T cell engaging cytokines (BiTEokines) and their high-throughput phenotypic screening, requiring just days for hit identification and the analysis of composition-function relationships. Using this approach, we identified CD19 × CD3 × IL12 compounds that exhibit ex vivo lytic activity comparable to current FDA-approved therapies for leukemia and correlated drug treatment with specific cell-cell contact, cytokine delivery, and leukemia cell lysis. Given the modular nature of these multivalent compounds and their rapid assembly/screening, we anticipate facile extension of this therapeutic approach to a wide range of immune cells, diseased cells, and soluble protein combinations in the future.

Priscilla Do

Lacey A Perdue

Andrew Chyong

Rae Hunter

Jodi Dougan

Curtis J Henry

Christopher C Porter

Erik C Dreaden

Rapid Assembly and Screening of Multivalent Immune Cell-Redirecting Therapies for Leukemia

白血病多价免疫细胞重定向疗法的快速组装与筛选

Cyclic peptides with engineered protein-binding activity have gained increasing attention for use in therapeutic and biotechnology applications. We describe the efficient isolation and characterization of cyclic peptide binders from genetically encoded combinatorial libraries using yeast surface display. Here, peptide cyclization is achieved by disuccinimidyl glutarate-mediated cross-linking of amine groups within a linear peptide sequence that is expressed as a yeast cell surface fusion. Using this approach, we first screened a library of cyclic heptapeptides using magnetic selection, followed by fluorescence activated cell sorting (FACS) to isolate binders for a model target (lysozyme) with low micromolar binding affinity (KD ∼ 1.2-3.7 μM). The isolated peptides bind lysozyme selectively and only when cyclized. Importantly, we showed that yeast surface displayed cyclic peptides can be used to efficiently obtain quantitative estimates of binding affinity, circumventing the need for chemical synthesis of the selected peptides. Subsequently, to demonstrate broader applicability of our approach, we isolated cyclic heptapeptides that bind human interleukin-17 (IL-17) using yeast-displayed IL-17 as a target for magnetic selection, followed by FACS using recombinant IL-17. Molecular docking simulations and follow-up experimental analyses identified a candidate cyclic peptide that likely binds IL-17 in its receptor binding region with moderate apparent affinity (KD ∼ 300 nM). Taken together, our results show that yeast surface display can be used to efficiently isolate and characterize cyclic peptides generated by chemical modification from combinatorial libraries.

Kaitlyn Bacon

Abigail Blain

Matthew Burroughs

Nikki McArthur

Balaji M. Rao

Stefano Menegatti

Isolation of Chemically Cyclized Peptide Binders Using Yeast Surface Display

利用酵母表面展示技术分离化学环化肽结合剂

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTACS Combinatorial Science: January, 1999–December, 2020M. G. Finn*M. G. FinnSchool of Chemistry and Biochemistry, School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332, United States*Email: [email protected]More by M. G. Finnhttp://orcid.org/0000-0001-8247-3108Cite this: ACS Comb. Sci. 2020, 22, 12, 667–668Publication Date (Web):December 14, 2020Publication History Published online14 December 2020Published inissue 14 December 2020https://pubs.acs.org/doi/10.1021/acscombsci.0c00181https://doi.org/10.1021/acscombsci.0c00181editorialACS PublicationsCopyright © 2020 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views2585Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (576 KB) Get e-AlertscloseSUBJECTS:Combinatorial chemistry,Combinatorial synthesis,Drug discovery,Materials,Testing and assessment Get e-Alerts

M. G. Finn

ACS Combinatorial Science: January, 1999–December, 2020

《ACS组合科学：1999年1月至2020年12月》

Desorption electrospray ionization-mass spectrometry (DESI-MS) was used as a high-throughput experimentation (HTE) tool to rapidly identify derivatives of the biobased platform molecule triacetic acid lactone (TAL). TAL is a platform molecule capable of conversion to a wide range of useful commodity chemicals, agrochemicals, and advanced pharmaceutical intermediates. In the present study, a diverse family of aldol reaction mixtures were prepared in high-density microtiter plates with a liquid handling robot, then printed with a pin tool onto a PTFE surface for analysis by DESI-MS. Our DESI-MS results indicate that aldol products of TAL were obtained for each substrate tested, in good agreement with previously reported TAL reactivity. These HTE experiments also revealed solvent-dependent reactivity trends that facilitated reaction scale up. Our findings suggest that DESI-MS analysis can rapidly inform the selection of optimal reaction conditions from a wide variety of conditions for scale up using continuous synthesis conditions.

H. Samuel Ewan

Shruti A. Biyani

Jaycie DiDomenico

David Logsdon

Tiago J. P. Sobreira

Larisa Avramova

R. Graham Cooks

David H. Thompson

Aldol Reactions of Biorenewable Triacetic Acid Lactone Precursor Evaluated Using Desorption Electrospray Ionization Mass Spectrometry High-Throughput Experimentation and Validated by Continuous Flow Synthesis

生物可再生三乙酸内酯前体的Aldol反应通过解吸电喷雾电离质谱高通量实验评估并经连续流动合成验证

A novel magnetic metal–organic framework (Fe3O4@GlcA@Cu-MOF) has been prepared and characterized by spectroscopic, microscopic, and magnetic techniques. This magnetically separable catalyst exhibited high catalytic activity for nitrile hydration and the ability to reduce isothiocyanates, isocyanates, and isocyanides with excellent activity and selectivity without any additional reducing agent.

Arash Ghorbani-Choghamarani

Zahra Taherinia

Fe3O4@GlcA@Cu-MOF: A Magnetic Metal–Organic Framework as a Recoverable Catalyst for the Hydration of Nitriles and Reduction of Isothiocyanates, Isocyanates, and Isocyanides

Fe3O4@GlcA@Cu-MOF：一种用于腈水合、异硫氰酸酯、异氰酸酯和异氰化物还原的可回收磁性金属有机框架催化剂

The power of ribosomes has increasingly been harnessed for the synthesis and selection of molecular libraries. Technologies, such as phage display, yeast display, and mRNA display, effectively couple genotype to phenotype for the molecular evolution of high affinity epitopes for many therapeutic targets. Genetic code expansion is central to the success of these technologies, allowing researchers to surpass the intrinsic capabilities of the ribosome and access new, genetically encoded materials for these selections. Here, we review techniques for the chemical expansion of genetically encoded libraries, their abilities and limits, and opportunities for further development. Importantly, we also discuss methods and metrics used to assess the efficiency of modification and library diversity with these new techniques.

Sabrina E. Iskandar

Victoria A. Haberman

Albert A. Bowers

Expanding the Chemical Diversity of Genetically Encoded Libraries

扩展遗传编码库的化学多样性

Thin-film continuous composition spreads of Fe–Co–O were fabricated by reactive cosputtering from elemental Fe and Co targets in reactive Ar/O2 atmosphere using deposition temperatures ranging from 300 to 700 °C. Fused silica and platinized Si/SiO2 strips were used as substrates. Ti and Ta were investigated as adhesion layer for Pt and the fabrication of the Fe–Co–O films. The thin-film composition spreads were characterized by high-throughput electron-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and optical transmission spectroscopy. The Fe-content ranged from 28 to 72 at. %. The spinel phases Fe2CoO4 and FeCo2O4 could be synthesized and stabilized at all deposition temperatures with a continuous variation in spinel composition in between. The dependence of the film surface microstructure on the deposition temperature and the composition was mapped. Moreover, the band gap values, ranging from 2.41 eV for FeCo2O4 to 2.74 eV for Fe2CoO4, show a continuous variation with the composition.

Tobias H. Piotrowiak

Xiao Wang

Lars Banko

Swati Kumari

Suchismita Sarker

Apurva Mehta

Alfred Ludwig

High-Throughput Characterization of (FexCo1–x)3O4 Thin-Film Composition Spreads

高通量表征(FexCo1–x)3O4薄膜成分分布

Abbreviation	ACS Comb. Sci.
Journal Impact	3.72

ISSN	2156-8944, 2156-8952
h-index	58

Publication Information	Publisher: American Chemical Society，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2011，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 10.80%
Average review cycle	网友分享经验：较慢,6-12周

ACS Combinatorial Science

Journal Citation Format

A journal article with 1 author

A journal article with 2 authors

A journal article with 3 authors

A journal article with 5 or more authors

Books Citation Format

Thesis Citation Format

Web sites Citation Format

Patent Citation Format

Staying up late manually editing references? ivySCI automatically matches journals and helps you generate references with a single click.

Share Submission Experience