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Showing 1–15 of 15 results
Advanced filters: Author: Christian Heinis Clear advanced filters

  • Cyclic peptides show promise for modulating difficult disease targets; however, they often cannot be administered orally. The authors developed a method to synthesize and screen large libraries of small cyclic peptides while enabling the simultaneous interrogation of activity and permeability. This approach was applied to the disease target thrombin to discover peptides with high affinity, stability and oral bioavailability of up to 18% in rats.

    • Manuel L. Merz
    • Sevan Habeshian
    • Christian Heinis
    ResearchOpen Access
    Nature Chemical Biology
    Volume: 20, P: 624-633

  • Inhibiting thrombosis without inducing bleeding is a major challenge for anticoagulant agents. Here the authors describe a synthetic FXIIa inhibitor able to efficiently prevent thrombosis in mice and suppress coagulation in artificial lungs in rabbits without increasing the risk of bleeding.

    • Jonas Wilbs
    • Xu-Dong Kong
    • Christian Heinis
    ResearchOpen Access
    Nature Communications
    Volume: 11, P: 1-13

  • A major challenge for the application of peptide therapeutics is their short half-lifein vivo. Here, the authors design peptide-fatty acid chimeras bearing an engineered linker that promotes albumin binding and allows longer circulation times of therapeutic peptides in animal models.

    • Alessandro Zorzi
    • Simon J. Middendorp
    • Christian Heinis
    ResearchOpen Access
    Nature Communications
    Volume: 8, P: 1-9

  • The application of macrocycles to previously undruggable targets has aroused a great deal of interest in this structural class. Recent studies advance our understanding of the way macrocycles bind protein targets and provide new strategies and tools to generate peptide-based macrocycles.

    • Christian Heinis
    News & Views
    Nature Chemical Biology
    Volume: 10, P: 696-698

  • Macrocycles have potential as therapeutics, but their libraries are currently not large enough for high-throughput screening. Here, the authors show a combinatorial approach to generate a library of almost 20’000 macrocycles by conjugating carboxylic-acid fragments to macrocyclic scaffolds, identifying nanomolar inhibitors against thrombin and binders of MDM2.

    • Sevan Habeshian
    • Manuel Leonardo Merz
    • Christian Heinis
    ResearchOpen Access
    Nature Communications
    Volume: 13, P: 1-14

  • Crosslinking within peptides containing two pairs of cysteines to form chemical bridges has now been shown to provide rapid access to thousands of different macrocyclic scaffolds in libraries that are easy to synthesize, screen and decode. Applying this strategy to phage-encoded libraries yielded binders with remarkable affinities despite the small molecular mass.

    • Sangram S. Kale
    • Camille Villequey
    • Christian Heinis
    Research
    Nature Chemistry
    Volume: 10, P: 715-723

  • Disulfide bonds formed between two cysteine residues are important in the folding and stability of proteins. Now, unnatural amino acids with side-chains that contain two thiol groups are described. Incorporation of these dithiol amino acids into a serine protease inhibitor and a nicotinic acetyl choline receptor antagonist is shown to increase their inhibitory activity.

    • Shiyu Chen
    • Ranganath Gopalakrishnan
    • Christian Heinis
    Research
    Nature Chemistry
    Volume: 6, P: 1009-1016

  • Yeast surface display technology enables real-time monitoring and effective screening of libraries of millions of disulfide-cyclised peptides against diverse protein targets. Selected ligands are characterised rapidly and quantitatively without the need for chemical synthesis and purification.

    • Sara Linciano
    • Ylenia Mazzocato
    • Alessandro Angelini
    ResearchOpen Access
    Nature Communications
    Volume: 16, P: 1-23

  • Tricyclic peptides have reduced conformational flexibility, making them well suited for ligand development. Researchers have now generated large combinatorial libraries of tricyclic peptides using a disulfide-directing motif. Screening these libraries discovered binders to challenging protein targets.

    • Christian Heinis
    News & Views
    Nature Chemical Biology
    Volume: 19, P: 799-800

  • 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
    News & Views
    Nature Chemistry
    Volume: 13, P: 512-513

  • Here the authors use phage display to develop cystine-knot peptides that inhibit the trimeric serine protease HTRA1. Structural and biochemical characterisation uncovered binding of the peptides to a cryptic pocket that locked the active site in a noncompetent state.

    • Yanjie Li
    • Yuehua Wei
    • Daniel Kirchhofer
    ResearchOpen Access
    Nature Communications
    Volume: 15, P: 1-17

  • Shimada et al. show that uncoordinated repair by base excision repair generates a lethal accumulation of DNA double-strand breaks at clustered lesions. Rapid conversion of oxidative DNA damage into fragmented chromosomes stems from TORC2 inhibition.

    • Kenji Shimada
    • Cleo V. D. Tarashev
    • Susan M. Gasser
    ResearchOpen Access
    Nature Communications
    Volume: 15, P: 1-20