Title: Inhibition of selectin binding

Abstract

This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

Inventors:

Nagy, Jon O ^[1]; Spevak, Wayne R ^[2]; Dasgupta, Falguni ^[3]; Bertozzi, Caroline ^[2]

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+ Show Inventor Affiliations

1. Rodeo, CA
2. Albany, CA
3. New Delhi, IN

Issue Date:

1999-01-01

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

OSTI Identifier:

872672

Patent Number(s):

5985852

Assignee:

Regents of University of California ()

Patent Classifications (CPCs):

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

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A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A61K31/7024 - Esters of saccharides
A61K9/1273 - {Polymersomes

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

A61P11/06 - Antiasthmatics
A61P29/00 - Non-central analgesic, antipyretic or anti-inflammatory agents, e.g antirheumatic agents
A61P35/04 - specific for metastasis
A61P43/00 - Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
A61P9/00 - Drugs for disorders of the cardiovascular system
A61P9/10 - for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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DOE Contract Number:  

AC03-76SF00098

Resource Type:

Patent

Country of Publication:

United States

Language:

English

Subject:

inhibition; selectin; binding; provides; compositions; inhibiting; cells; expressing; p-; l-selectin; surface; corresponding; ligand; covalently; crosslinked; lipid; composition; prepared; saccharides; acidic; separate; lipids; interposed; inhibit; achieved; effective; oligosaccharide; concentration; 10; fold; below; free; saccharide; selectins; involved; recruiting; sites; injury; scan; palliate; inflammatory; immunological; conditions; recruiting cells; provides compositions; selectin binding; separate lipids; oligosaccharide concentration; expressing p-; fold below; free saccharide; lipid composition; effective oligosaccharide; covalently crosslinked; crosslinked lipid; corresponding ligand; immunological conditions; inhibit binding; /514/424/999/