| Autor: |
Chinoy, Zoeisha S., Friscourt, Frédéric, Capicciottia, Chantelle J, Chiu, Philip, Boons, Geert-Jan |
| Přispěvatelé: |
Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Popis: |
Complex N-glycans of glycoproteins of the zona pellucida (ZP) of human oocytes have been implicated in the binding of spermatozoa. The termini of these unusual bi-, tri-, and tetra-antennary N-glycans consist of the tetrasaccharide sialyl-Lewisx (SLex), which was previously identified as the minimal epitope for sperm binding. We describe here the chemo-enzymatic synthesis of highly complex tri-antennary N-glycans derived from ZP carrying SLex moieties at the C-2 and C-2' arm and a sialyl-Lewisx-Lewisx (SLex-Lex) residue at the C-6 antenna and two closely related analogs. The compounds were examined for their ability to inhibit the interaction of human sperm to ZP. It was found that the SLex-Lex moiety is critical for inhibitory activity, whereas the other SLex moieties exerted minimal effect. Further studies with SLex-Lex and SLex showed that the extended structure is the more potent inhibitor. In addition, trivalent SLex-Lex and SLex were prepared which showed greater inhibitory activity compared to their monovalent counterparts. Our studies show that although SLex can inhibit the binding of spermatozoa, presenting this epitope in the context of a complex N-glycan results in a loss of inhibitory potential, and in this context only SLex-Lex can make productive interactions. It is not the multivalent display of SLex on a multi-antennary glycan but the presentation of multiple SLex-Lex on the various glycosylation sites of ZP that accounts for high avidity binding. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
