# 3-O-sulfation of heparan sulfate as a regular of protein function

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2022 · $451,658

## Abstract

Project summary/abstract
Heparin is a highly sulfated carbohydrate produced by mast cells that is widely used as an anticoagulant
to prevent deep vein thrombosis, pulmonary embolism and arterial thromboembolism. Heparan sulfate
(HS) is structurally related to heparin and decorates the surface of all most all human cells. It interacts
with a multitude of proteins including chemokines and cytokines; blood coagulation factors; growth
factors and morphogens, proteins involved in complement activation, and cell adhesion and signaling
proteins. HS has been implicated in human diseases such as vascular diseases, inflammation,
infections and neurodegeneration. It has been postulated that HS encodes information by an ability to
recruit proteins in a context-dependent manner. Although the “HS-sulfate code” hypothesis is
conceptually appealing, little is known about the ligand specificities of HS binding proteins and the
substrate specificities of HS-biosynthetic enzymes. As a result, it is not known whether isoforms of HS
biosynthetic enzymes can create distinctive epitopes that in a cellular context can recruit specific HS-
binding proteins. An understanding of the specificities of HS binding also offers opportunities to develop
therapeutic modalities.
In this program, chemical and chemo-enzymatic methodologies will be developed that will make it
possible to prepare a focused library of biologically relevant HS epitopes with and without a 3-O-sulfate
moiety. These compounds will be used to develop an HS-microarray to establish ligand requirement of
HS-binding proteins. Compounds of interest will be further explored for their ability to interfere in the
binding and cellular activation of endothelial cells. We will focus on HS-binding proteins involved in blood
coagulation, inflammation and vascular disease. The established structure-activity relationships are
expected to provide therapeutic lead compounds. The HS-microarray will also be used as a general
platform to discover and characterize HS-binding proteins requiring a 3-O-sulfate. In addition, the
synthetic compounds will be used to define substrate requirements of the various 3-O-sulfotransferases.
Collectively, our studies will address the question of whether isoforms of 3-O-sulfotransferases can
create distinctive epitopes that can recruit specific HS-binding proteins, to mediate various biological
processes.
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## Key facts

- **NIH application ID:** 10400697
- **Project number:** 5R01HL151617-03
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Geert-Jan Boons
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $451,658
- **Award type:** 5
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400697

## Citation

> US National Institutes of Health, RePORTER application 10400697, 3-O-sulfation of heparan sulfate as a regular of protein function (5R01HL151617-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10400697. Licensed CC0.

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