PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

Article Article scientifique Article PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins eng 2020 author Farrera Soler Lluc 837562 author Daguer Jean Pierre 809701 author Raunft Patrick 923585 author Barluenga Badiola Sofia 810177 author Imberty Anne author Winssinger Nicolas 769664 115458 10.1016/j.bmc.2020.115458 0968-0896 https://linkinghub.elsevier.com/retrieve/pii/S0968089620302728 Selections from dynamic combinatorial libraries (DCL) benefit from the dynamic nature of the library that can change constitution upon addition of a selection pressure, such as ligands binding to a protein. This technology has been predominantly used with small molecules interacting with each other through reversible covalent interaction. However, application of this technology in biomedical research and drug discovery has been limited by the reversibility of covalent exchange and the analytical deconvolution of small molecule fragments. Here we report a supramolecular approach based on the use of a constant short PNA tag to direct the combinatorial pairing of fragment. This PNA tag yields fast exchange kinetics, while still delivering the benefits of cooperativity, and provides favourable properties for analytical deconvolution by MALDI. A selection from >6,000 assemblies of glycans (mono-, di-, tri-saccharides) targeting AFL, a lectin from pathogenic fungus, yielded a 95 nM assembly, nearly three orders of magnitude better in affinity than the corresponding glycan alone (41 µM). Dewey 540 36 Département de chimie organique 141 false 762 Groupe Winssinger Bioorganic & Medicinal Chemistry 28 10 dc51abda-ba3a-4f3d-b24c-3ce6babc4874 Article (Published version) Restricted 1-s2.0-S0968089620302728-main.pdf 4522807 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

Title	Published in	Access level	OA Policy	Year	Views	Downloads

PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins	Bioorganic & Medicinal Chemistry			2020	415	3

Archive ouverte UNIGE

Raunft, Patrick