La Jolla Cancer Research Foundation

The Burnham Institute

Integra Lifesciences Corporation

La Jolla Cancer Research Institute

Michael D Pierschbacher

Erkki I Ruoslahti

William S Craig

Soan Cheng

Juerg F Tschopp

David S Lukeman

Cyril J Honsik

Lisa B Dreisbach

Eric I Ruoslahti

Daniel G Mullen

Edward G Hayman

Shoukat Dedhar

James W Polarek

Ralph-Heiko Mattern

John J Grzesiak

Timothy Irvin Malaney

Kurt R Gehlsen

Daniel Kirchhofer

Jose Cardenas

Marianne P Petrica

Eric I Rudslahti

Fred Cahn

Novel synthetic Arg-Gly-Asp containing peptides which have high affinity and specificity for their receptors by virtue of restrictions on their stereochemical conformation. Such restrictions can be provided by cyclization, by inclusion into a constraining conformational structure such as a helix, by providing an additional chemical structure such as an amide or an enantiomer of a naturally occurring amino acid, or by other methods. In particular, there are provided cyclic peptides having increased affinity and selectivity for the certain receptors over that of linear, Arg-Gly-Asp-containing synthetic peptides.

Conformationally stabilized cell adhesion peptides

Compositions of cross-linked collagen and a glycosaminoglycan are provided which retain characteristics rendering them useful as tissue engineering matrices or scaffolds following terminal sterilization. Also provided are methods for producing these compositions and terminally sterilized matrices or scaffolds from these compositions as well as methods of using these matrices or scaffolds as tissue engineering devices.

Collagen/glycosaminoglycan matrix stable to sterilizing by electron beam radiation

The invention provides cyclic peptides which inhibit platelet aggregation without causing prolonged bleeding time. The invention provides RGD or KGD containing peptides which are cyclized and contain hydrophobic amino acids adjacent to the carboxy terminus of the RGD sequence. Peptides of this nature are also provided which contain in addition to the hydrophobic amino acid an adjacent positively charged amino acid. Such peptides have a high affinity for the receptor IIb/IIIa and a low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

Method and composition for treating thrombosis

The invention provides cyclic peptides which inhibit platelet aggregation without causing prolonged bleeding time. The invention provides RGD or KGD containing peptides which are cyclized and contain hydrophobic moieties adjacent to the carboxy terminus of the RGD sequence. Peptides of this nature are also provided which contain in addition to the hydrophobic. moiety an adjacent positively charged moiety. Such peptides have a high affinity for the receptor IIb/IIIa and a low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

Method for the isolation and characterization of a 140,000 dalton cell surface glycoprotein with the properties expected of a fibronectin receptor is described.

Isolation and use fibronectin receptor

The peptide X-Arg-Gly-Asp-R-Y wherein X is H or at least one amino acid and Y is OH or at least one amino acid, and R is an amino acid selected from Thr or Cys, or other amino acid, having the same cell-attachment activity as fibronectin and the peptide X-Arg-Gly-Asp-Ser-Y, wherein X and Y, having said activity are disclosed.

Tetrapeptide

The invention provides RGD containing peptides which are cyclized and contain hydrophobic moieties adjacent the carboxy terminus of the RGD sequence. Such peptides have an high affinity for the receptor IIb/IIIa and low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.

Novel synthetic Arg-Gly-Asp-containing peptides which have high affinity and specificity for their receptors by virtue of restrictions on their stereochemical conformation. Such restrictions can be provided by cyclization, by inclusion into a constraining conformational structure such as a helix, by providing an additional chemical structure such as an amide or an enantiomer of a naturally occuring amino acid, or by other methods. In particular, there is provided a cyclic peptide having increased affinity and selectivity for the vitronectin receptor over that of linear, Arg-Gly-Asp-containing synthetic peptides.

A conjugate of a synthetic polypeptide containing RGD or (dR) GD and a biodegradable polymer, such as hyaluronic acid or chondroitin sulfate is disclosed. Methods of making the conjugate and using it to aid wound healing by providing a temporary matrix are disclosed.

Growing community of inventors

San Diego, CA, United States of America

Michael D Pierschbacher