Combinatorial libraries

Definition

Combinatorial libraries are collections of chemical compounds, small molecules or macromolecules such as proteins, synthesized by combinatorial chemistry, in which multiple different combinations of related chemical species are reacted together in similar chemical reactions. Chemical synthesis methods are used to generate large groups of compounds that can themselves be elaborated in a similar combinatorial fashion.

Latest Research and Reviews

  • Research | | open

    Encoded Library Technology (ELT) has streamlined the identification of chemical ligands for protein targets in drug discovery. Here, the authors optimize the ELT approach to screen multiple proteins in parallel and identify promising targets and antibacterial compounds for S. aureus, A. baumannii and M. tuberculosis.

    • Carl A. Machutta
    • , Christopher S. Kollmann
    • , Kenneth E. Lind
    • , Xiaopeng Bai
    • , Pan F. Chan
    • , Jianzhong Huang
    • , Lluis Ballell
    • , Svetlana Belyanskaya
    • , Gurdyal S. Besra
    • , David Barros-Aguirre
    • , Robert H. Bates
    • , Paolo A. Centrella
    • , Sandy S. Chang
    • , Jing Chai
    • , Anthony E. Choudhry
    • , Aaron Coffin
    • , Christopher P. Davie
    • , Hongfeng Deng
    • , Jianghe Deng
    • , Yun Ding
    • , Jason W. Dodson
    • , David T. Fosbenner
    • , Enoch N. Gao
    • , Taylor L. Graham
    • , Todd L. Graybill
    • , Karen Ingraham
    • , Walter P. Johnson
    • , Bryan W. King
    • , Christopher R. Kwiatkowski
    • , Joël Lelièvre
    • , Yue Li
    • , Xiaorong Liu
    • , Quinn Lu
    • , Ruth Lehr
    • , Alfonso Mendoza-Losana
    • , John Martin
    • , Lynn McCloskey
    • , Patti McCormick
    • , Heather P. O’Keefe
    • , Thomas O’Keeffe
    • , Christina Pao
    • , Christopher B. Phelps
    • , Hongwei Qi
    • , Keith Rafferty
    • , Genaro S. Scavello
    • , Matt S. Steiginga
    • , Flora S. Sundersingh
    • , Sharon M. Sweitzer
    • , Lawrence M. Szewczuk
    • , Amy Taylor
    • , May Fern Toh
    • , Juan Wang
    • , Minghui Wang
    • , Devan J. Wilkins
    • , Bing Xia
    • , Gang Yao
    • , Jean Zhang
    • , Jingye Zhou
    • , Christine P. Donahue
    • , Jeffrey A. Messer
    • , David Holmes
    • , Christopher C. Arico-Muendel
    • , Andrew J. Pope
    • , Jeffrey W. Gross
    •  & Ghotas Evindar
  • Research | | open

    Identification of inhibitors can be accelerated by using the target as a template for ligand formation. Here the authors show that DNA-functionalised magnetic nanoparticles guide templating of G-quadruplex binding c-MYC inhibitors from an array of building blocks, and can be isolated by magnetic decanting.

    • Deepanjan Panda
    • , Puja Saha
    • , Tania Das
    •  & Jyotirmayee Dash
  • Research | | open

    Diversity-oriented synthesis is useful for generating complex molecular structures occupying diverse molecular space. Here the authors report a strategy to access libraries of privileged heterocyclic structures, and furthermore identify an inhibitor of LRS–RagD protein–protein interaction.

    • Jonghoon Kim
    • , Jinjoo Jung
    • , Jaeyoung Koo
    • , Wansang Cho
    • , Won Seok Lee
    • , Chanwoo Kim
    • , Wonwoo Park
    •  & Seung Bum Park
  • Research |

    A high-throughput virtual screening approach is used to select molecules with efficient, thermally activated delayed fluorescence. The good performance of several selected emitters in organic LED applications has also been confirmed experimentally.

    • Rafael Gómez-Bombarelli
    • , Jorge Aguilera-Iparraguirre
    • , Timothy D. Hirzel
    • , David Duvenaud
    • , Dougal Maclaurin
    • , Martin A. Blood-Forsythe
    • , Hyun Sik Chae
    • , Markus Einzinger
    • , Dong-Gwang Ha
    • , Tony Wu
    • , Georgios Markopoulos
    • , Soonok Jeon
    • , Hosuk Kang
    • , Hiroshi Miyazaki
    • , Masaki Numata
    • , Sunghan Kim
    • , Wenliang Huang
    • , Seong Ik Hong
    • , Marc Baldo
    • , Ryan P. Adams
    •  & Alán Aspuru-Guzik
    Nature Materials 15, 1120–1127
  • Research |

    A small molecule identified from high-throughput screening and optimization specifically stabilizes a disease-linked CLRN1 protein, delivering it to its site of action at the plasma membrane and preserving hearing in a new mouse model for Usher syndrome type III.

    • Kumar N Alagramam
    • , Suhasini R Gopal
    • , Ruishuang Geng
    • , Daniel H-C Chen
    • , Ina Nemet
    • , Richard Lee
    • , Guilian Tian
    • , Masaru Miyagi
    • , Karine F Malagu
    • , Christopher J Lock
    • , William R K Esmieu
    • , Andrew P Owens
    • , Nicola A Lindsay
    • , Krista Ouwehand
    • , Faywell Albertus
    • , David F Fischer
    • , Roland W Bürli
    • , Angus M MacLeod
    • , William E Harte
    • , Krzysztof Palczewski
    •  & Yoshikazu Imanishi

News and Comment

  • News and Views |

    The quantitative self-assembly of mechanically interlocked molecules in water, instead of organic solvents, opens up the possibility of such systems being used in a biological context where their functions can be interfaced with biomolecular systems.

    • Linyi Bai
    •  & Yanli Zhao
    Nature Chemistry 7, 944–945
  • Comments and Opinion |

    Jeffrey Bode from ETH Zürich talks with Nature Chemistry about his group's work on synthetic fermentation, and how he hopes it could bring the power of chemical synthesis into the hands of citizen scientists.

    Nature Chemistry 6, 846–847
  • News and Views |

    The generation of chemical libraries for screening is a key part of the drug discovery process. Now, two studies describe attempts to combine features of natural product biosynthesis into the creation of libraries with the aim of mimicking nature's success at the production of bioactive molecules.

    • Derek B. Lowe
    Nature Chemistry 6, 851–852
  • News and Views |

    A high-throughput approach combining combinatorial deposition of materials with parallel blow-forming speeds up the discovery rate of bulk metallic glasses that can be easily formed into complex shapes.

    • Dan B. Miracle
    Nature Materials 13, 432–433