Combinatorial libraries

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 Access

    Angiotensin converting enzyme 2 (ACE2) has been identified as a cardiovascular disease biomarker and the primary receptor utilized by SARS-CoV-2, but developing serum-stable, selective and high-affinity binders for this target is challenging. Here, the authors use affinity selection-mass spectrometry to identify multiple high affinity ACE2-binding peptides from canonical and noncanonical peptidomimetic libraries containing 200 million members.

    • Genwei Zhang
    • , Joseph S. Brown
    •  & Bradley L. Pentelute
  • Reviews |

    DNA-encoded chemical libraries (DECLs) are used in the discovery of small molecules with potential therapeutic benefit. In this Primer, Satz et al. describe the best practices for DECL synthesis, selection and analysis, as well as requirements to enhance reproducibility between and within groups.

    • Alexander L. Satz
    • , Andreas Brunschweiger
    •  & Jörg Scheuermann
  • Research |

    DNA-encoded libraries facilitate the discovery of ligands that interact with biomolecules but such technologies do not take full advantage of the principles of Darwinian selection. Now, libraries of conformationally constrained peptides (Dsuprabodies) have been assembled using a strategy that allows for iterative cycles of selection, amplification and diversification. This method was validated with selections against streptavidin and PD-L1.

    • Balayeshwanth R. Vummidi
    • , Lluc Farrera-Soler
    •  & Nicolas Winssinger
  • Research
    | Open Access

    Advanced glycation end-products (AGEs), such as methylglyoxal-derived hydroimidazolone isomer (MGH-1), are associated with disease and age-related disorders, and occur spontaneously, so it is unclear why specific protein sites become modified with specific AGEs. Here, the authors use a combinatorial peptide library to determine the chemical features that favour MGH-1 formation for short peptides and demonstrate a key role of tyrosine in this process.

    • Joseph M. McEwen
    • , Sasha Fraser
    •  & Rebecca A. Scheck

News and Comment

  • News & Views |

    Phage display enables screening of billions of peptides comprised mainly of natural amino acids. Now, a method to attach and encode a range of structurally diverse compounds has been reported. This method can expand the chemical space covered by phage display peptide libraries.

    • Christian Heinis
    Nature Chemistry 13, 512-513
  • News & Views |

    Directed evolution on the yeast cell surface enables the discovery of sortase variants with altered specificity capable of modifying Aβ peptides under physiologically relevant conditions.

    • James A. Van Deventer
  • News & Views |

    High-throughput screening of solvothermal crystallization conditions for MOFs and other solids may receive a boost from the application of 3D printing techniques to low-cost, disposable pressure vessels.

    • Ian D. Williams
    Nature Chemistry 6, 953-954
  • News & 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
  • News & Views |

    Systems biology methods accumulate a vast array of information to generate hypotheses and discover new cellular relationships. A combination of 'omics' technologies now provides important proof of biochemical predictions and creates new opportunities for understanding cellular functional architecture.

    • Andreas Schmid
    •  & Lars M Blank