Children's Medical Center Corporation

Leland Stanford Junior University

University of Iowa Research Foundation

Merton Bernfield

Scott Saunders

Masato Kato

Richard L Gallo

Robert J Linhardt

Yeong Shik Kim

William E Benitz

Ofer Reizes

A purified mammalian proteoglycan, and genetic information encoding such proteoglycans, having a core polypetide molecular weight of about 30 kD to about 35 kD, and comprising a hydrophilic amino terminal extracellular region, a hydrophilic carboxy terminal cytoplasmic region, a transmembrane hydrophobic region between said cytoplasmic and extracellular regions, a protease susceptible cleavage sequence extracellularly adjacent the transmembrane region of the peptide, and at least one glycosylation site for attachment of a heparan sulfate chain to said extracellular region, said glycosylation site comprising a heparan sulfate attachment sequence represented by a formula Xac-Z-Ser-Gly-Ser-Gly (SEQ ID NO: 44), where Xac represents an amino acid residue having an acidic sidechain, and Z represents from 1 to 10 amino acid residues. Additional peptides having this glycosylation site and genetic information useful for preparing a number of variations based on this glycosylation site are also provided.

Construction and use of synthetic constructs encoding syndecan

A purified mammalian proteoglycan, and genetic information encoding such proteoglycans, having a core polypetide molecular weight of about 30 kD to about 35 kD, and comprising a hydrophilic amino terminal extracellular region, a hydrophilic carboxy terminal cytoplasmic region, a transmembrane hydrophobic region between said cytoplasmic and extracellular regions, a protease susceptible cleavage sequence extracellularly adjacent the transmembrane region of the peptide; and at least one glycosylation site for attachment of a heparan sulfate chain to said extracellular region, said glycosylation site comprising a heparan sulfate attachment sequence represented by a formula Xac-Z-Ser-Gly-Ser-Gly, where Xac represents an amino acid residue having an acidic sidechain, and Z represents from 1 to 10 amino acid residues. Additional peptides having this glycosylation site and genetic information useful for preparing a number of variations based on this glycosylation site are also provided.

Synthetic constructs encoding syndecan

Methods and reagents for regulating obesity

The present invention is based on the unexpected discovery that a molecule having as its major repeating units N-acetylglucosamine alternating in sequence with 2-O-sulfated uronic acid, inhibits FGF mitogenicity, and thus is useful in inhibiting angiogenesis. Additionally, the molecule has low toxicity and inhibits FGF mitogenicity without affecting anticoagulant activity. One preferred molecule is a glycosaminoglycan such as archaran sulfate. The molecules are in pharmaceutical compositions that can be used in the treatment of diseases which are angiogenesis-dependent.

Angiogenesis inhibitors and use thereof

The membrane permeating antibacterial peptide, PR-39, previously found only in the intestine, was purified from wound fluid and shown to possess syndecan-1 and syndecan-4 inductive activity specifically in mesenchymal cells. This is a newly recognized function that defines peptide containing syndecan-inducing activity, and that are known as synducins. Therefore a molecule with both antimicrobial and synducin activities is deposited in wounds where it can simultaneously reduce infection and influence the action of growth factors, matrix components, and other cellular effectors involved in wound repair. Synducins, including PR-39, and derivatives thereof, is therefore useful in the modulation of wound healing, as well as other disorders involving mesenchymal cells and cell surface molecular interaction, including metastatic disease, angiogenesis, restenosis, stasis or decubitis ulcers, and prevention of keloids.

Synducin mediated modulation of tissue repair

A purified mammalian proteoglycan, and genetic information encoding such proteoglycans, having a core polypetide molecular weight of about 30 kD to about 35 kD, and comprising a hydrophilic amino terminal extracellular region, a hydrophilic carboxy terminal cytoplasmic region, a transmembrane hydrophobic region between said cytoplasmic and extracellular regions, a protease susceptible cleavage sequence extracellularly adjacent the transmembrane region of the peptide, and at least one glycosylation site for attachment of a heparan sulfate chain to said extracellular region, said glycosylation site comprising a heparan sulfate attachment sequence represented by a formula Xac-Z-Ser-Gly-Ser-Gly, where Xac represents an amino acid residue having an acidic sidechain, and Z represents from 1 to 10 amino acid residues. Additional peptides having this glycosylation site and genetic information useful for preparing a number of variations based on this glycosylation site are also provided.

An epithelium-derived inhibitor of the growth of smooth muscle cells is disclosed along with methods for purifying this substance. As initially isolated, the inhibitor comprises a heparan sulfate proteoglycan having a buoyant density of less than 1.4 g/ml which releases a glycosaminoglycan chain having a molecular weight of about 55,000 to 75,000 on protease cleavage. Growth inhibiting activity is found in the glycosaminoglycan chain and in glycosaminoglycan fragments derived therefrom. Use of a dialyzable detergent in purification steps greatly aids in the handling and purification of the inhibitor. The inhibitor can be used in a variety of techniques for inhibiting the growth of smooth muscle cells, both in vivo and in vitro.

Growing community of inventors

Boston, MA, United States of America

Merton Bernfield