UNIGE document Scientific Article
previous document  unige:134730  next document
add to browser collection
Title

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

Authors
Imberty, Anne
Published in Bioorganic & Medicinal Chemistry. 2020, vol. 28, no. 10, 115458
Abstract 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).
Identifiers
Full text
Structures
Research group Groupe Winssinger
Citation
(ISO format)
FARRERA SOLER, Lluc et al. PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins. In: Bioorganic & Medicinal Chemistry, 2020, vol. 28, n° 10, p. 115458. doi: 10.1016/j.bmc.2020.115458 https://archive-ouverte.unige.ch/unige:134730

172 hits

3 downloads

Update

Deposited on : 2020-04-20

Export document
Format :
Citation style :