# Sulfated Poly-Amido-Saccharide (sulPAS) Biomaterials as Anticoagulants

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $553,824

## Abstract

PROJECT SUMMARY/ABSTRACT
 This proposal describes a novel biomaterial and synthetic anticoagulant. Anticoagulants are a mainstay
of modern surgery and of clotting disorder management such as venous thrombosis, yet performance and
supply limitations exist for the most widely used agent - heparin. Specifically, heparin’s heterogeneous
structure affords highly variable activity, patient-dependent dose-responses, and life-threatening side effects
such as heparin induced thrombocytopenia. Additionally, African Swine Fever (a double-stranded DNA virus
in the Asfarviridae family) has wiped out over one-quarter of the world’s pig population leading to global
shortages, contamination issues, and the need for alternatives – i.e., anticoagulants of non-animal origin.
We propose the use of disulfated poly-amido-saccharides (PASs) as heparin mimetics. PASs are new well-
defined, enantiopure carbohydrate polymers that are stereochemically defined, hydrophilic, and possess
pyranose rings in the backbone. PASs are efficiently synthesized by the anionic ring-opening polymerization
reaction of a β-lactam sugar monomer in high-yields with batch-to-batch consistency, defined molecular
weights, and low polydispersity. Sulfation of PAS yields such unique heparin mimetics. Herein, we describe
the novel synthesis along with detailed in vitro and ex vivo mechanism-of-action and in vivo efficacy studies.
The proposed experiments will define the molecular and structural basis for anticoagulant activity
of disulfated PAS (disulPAS) and will test the hypothesis that regioselectively functionalized
disulPASs will be: 1) efficacious in vivo with activity equivalent to or better than low molecular
weight heparin (LMWH); and 2) neutralized by protamine sulfate unlike synthetic Fondaparinux.
Further, sulPAS anticoagulant activity will depend on the number and the position of sulfate
functionalization and not be associated with heparin-induced thrombocytopenia. Importantly,
substantial preliminary data support the proposed studies, well-characterized materials and rigorous
experimental designs are established, and essential cross-disciplinary collaborations and expertise are in
place to address the hypotheses. The specific aims of this five-year proposal are as follows. Aim 1
synthesizes and characterizes new regioselectively disulfated PAS. Aim 2 evaluates the in vitro/ex vivo
anticoagulant activity and determines the mechanism of action (MOA) of disulfated PASs. Aim 3 defines the
pharmacokinetic and pharmacodynamic profile of lead disulPAS candidates and efficacy in rodent models of
thromboprophylaxis and bleeding risk.

## Key facts

- **NIH application ID:** 10499604
- **Project number:** 1R01HL164650-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Elliot Chaikof
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $553,824
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499604

## Citation

> US National Institutes of Health, RePORTER application 10499604, Sulfated Poly-Amido-Saccharide (sulPAS) Biomaterials as Anticoagulants (1R01HL164650-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10499604. Licensed CC0.

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