# A Human Salivary Glycome Discovery Platform for Interrogating Glycan Function in Oral Innate Immunity

> **NIH NIH R43** · NATGLYCAN, LLC · 2022 · $314,971

## Abstract

Project summary
The oral cavity is the first critical interface between potentially harmful substances or pathogens in the host
environment, and evolution of the adaptive and innate immune defense mechanisms to inactivate or eliminate
pathogenic microbes has to a great extent used protein-glycan interaction. The glycan components of saliva
have been shown to play important roles in biological and immunological aspects of oral host-microbe, microbe-
host, and microbe-microbe interactions, and we have shown that glycans attached salivary glycoproteins can
act as a first line of host defense in the human mouth and that glycan recognition contributes to both colonization
and clearance of oral microbes. A revolutionary innovation in studies of protein-glycan interactions was the
glycan microarray, which permitted the identification glycan ligands for biologically relevant glycan binding
proteins (GBP) by their simultaneous interrogation with hundreds of glycan structures printed on a microscope
slide. Comparisons of the structures of bound and non-bound glycans reveal the glycan specificity of GBP, and
this information is used in further biological studies to understand the biological function of GBP. In this project
we will generate a glycan microarray composed of glycans that represent the salivary glycome, i.e. the entirety
of glycans in saliva. This will be accomplished by first producing a library of purified, naturally occurring N- and
O-linked glycans released from 10 liters of pooled human saliva by an innovative process for the Oxidative
Release of Natural Glycans (ORNG) using simple household bleach. The library of glycans will be printed as a
glycan microarray and interrogated with oral streptococcal glycan-binding adhesins to identify their
corresponding natural high-affinity glycan ligands. We will use our recently established toolbox of streptococcal
serine-rich-repeat protein adhesins that each contain sialic-acid-binding Siglec-like domains of differing
specificity for subtypes of sialic acids in the wider context of their underlying subterminal glycans. For some of
these lectins, the natural glycan ligands were not identified using currently available arrays, presumably due to
the absence of their corresponding natural glycan ligands presented in the assays to date. Since these are lectins
expressed by oral microbes, we anticipate that there is a high probability that their natural glycan ligands will be
present in the glycome of human saliva, the natural biological fluid in which these microorganisms thrive. This
Phase I project should provide an example of how a complete glycome can be used as a discovery platform for
identifying a novel protein-glycan interaction. Once the details of the structure of the glycan ligand are defined,
the information will become intellectual property that will lead to strategies to therapeutically interfere with
microbial colonization or pathogen infection in the mouth and beyond. This platform for und...

## Key facts

- **NIH application ID:** 10484608
- **Project number:** 1R43DE031990-01
- **Recipient organization:** NATGLYCAN, LLC
- **Principal Investigator:** David Fletcher Smith
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $314,971
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484608

## Citation

> US National Institutes of Health, RePORTER application 10484608, A Human Salivary Glycome Discovery Platform for Interrogating Glycan Function in Oral Innate Immunity (1R43DE031990-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10484608. Licensed CC0.

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