Premium
Divalent Sialylated Precision Glycooligomers Binding to Polyomaviruses and the Effect of Different Linkers
Author(s) -
Baier Mischa,
Rustmeier Nils H.,
Harr Joachim,
Cyrus Norbert,
Reiss Guido J.,
Grafmüller Andrea,
Blaum Bärbel S.,
Stehle Thilo,
Hartmann Laura
Publication year - 2019
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201800426
Subject(s) - linker , chemistry , glycan , ligand (biochemistry) , divalent , sialic acid , capsid , biophysics , biochemistry , combinatorial chemistry , glycoprotein , receptor , biology , organic chemistry , computer science , gene , operating system
Divalent precision glycooligomers terminating in N ‐acetylneuraminic acid (Neu5Ac) or 3′‐sialyllactose (3′‐SL) with varying linkers between scaffold and the glycan portions are synthesized via solid phase synthesis for co‐crystallization studies with the sialic acid‐binding major capsid protein VP1 of human Trichodysplasia spinulosa ‐associated Polyomavirus. High‐resolution crystal structures of complexes demonstrate that the compounds bind to VP1 depending on the favorable combination of carbohydrate ligand and linker. It is found that artificial linkers can replace portions of natural carbohydrate linkers as long as they meet certain requirements such as size or flexibility to optimize contact area between ligand and receptor binding sites. The obtained results will influence the design of future high affinity ligands based on the structures presented here, and they can serve as a blueprint to develop multivalent glycooligomers as inhibitors of viral adhesion.