Biocatalysis versus Molecular Recognition in Sialoside-Selective Neuraminidase Biosensing

Israel Alshanski, Suraj Toraskar, Ariel Shitrit, Daniel Gordon-Levitan, Prashant Jain, Raghavendra Kikkeri*, Mattan Hurevich*, Shlomo Yitzchaik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Sialic acid recognition and hydrolysis are essential parts of cellular function and pathogen infectivity. Neuraminidases are enzymes that detach sialic acid from sialosides, and their inhibition is a prime target for viral infection treatment. The connectivity and type of sialic acid influence the recognition and hydrolysis activity of the many different neuraminidases. The common strategies to evaluate neuraminidase activity, recognition, and inhibition rely on extensive labeling and require a large amount of sialylated glycans. The above limitations make the effort of finding viral inhibitors extremely difficult. We used synthetic sialylated glycans and developed a label-free electrochemical method to show that sialoside structural features lead to selective neuraminidase biosensing. We compared Neu5Ac to Neu5Gc sialosides to evaluate the organism-dependent neuraminidase selectivity-sensitivity relationship. We demonstrated that the type of surface and the glycan monolayer density direct the response to either binding or enzymatic activity. We proved that while the hydrophobic glassy carbon surface increases the interaction with the enzyme hydrophobic interface, the negatively charged interface of the lipoic acid monolayer on gold repels the protein and enables biocatalysis. We showed that the sialoside monolayers can serve as tools to evaluate the inhibition of neuraminidases both by biocatalysis and molecular recognition.

Original languageAmerican English
Pages (from-to)605-614
Number of pages10
JournalACS Chemical Biology
Volume18
Issue number3
DOIs
StatePublished - 17 Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.

Fingerprint

Dive into the research topics of 'Biocatalysis versus Molecular Recognition in Sialoside-Selective Neuraminidase Biosensing'. Together they form a unique fingerprint.

Cite this