La Jolla Cancer Research Center

La Jolla Cancer Research Foundation

Daniel G Mullen

Soan Cheng

Juerg F Tschopp

Ronald Ingram

Michael D Pierschbacher

William S Craig

Erkki I Ruoslahti

James W Polarek

Lin-Shu Liu

James R Glass

Kenneth T Dickerson

Jose Cardenas

The present invention provides antithrombotic agents useful for the management of cardiovascular disease. The agents of the subject invention are novel cyclic peptides encompassed by the following formula:

Antithrombotic agents and methods of use

The present invention provides Arg-Gly-Asp peptides that can alter the binding of osteoclasts to a matrix such as bone or can selectively alter integrin receptor binding. The invention also provides methods of using the Arg-Gly-Asp peptides to alter .alpha..sub.v .beta..sub.3 integrin receptor-mediated binding of a cell such as an osteoclast, endothelial cell or smooth muscle cell to a matrix. The invention further provides methods for ameliorating the severity of a pathology characterized, in part, by an undesirable level of bone resorption, angiogenesis or restenosis in a subject.

Peptides for altering bone resorption, angiogenesis and restenosis

The present invention provides Arg--Gly--Asp peptides that can alter the binding of osteoclasts to a matrix such as bone or can selectively alter integrin receptor binding. The invention also provides methods of using the Arg--Gly--Asp peptides to alter .alpha..sub.V .beta..sub.3 integrin receptor-mediated binding of a cell such as an osteoclast, endothelial cell or smooth muscle cell to a matrix. The invention further provides methods for ameliorating the severity of a pathology characterized, in part, by an undesirable level of bone resorption, angiogenesis or restenosis in a subject.

Peptides useful for altering bone resorption

Use of peptides for altering bone resorption

The present invention provides Arg--Gly--Asp peptides that can alter the binding of osteoclasts to a matrix such as bone or can selectively alter integrin receptor binding. The invention also provides methods of using the Arg--Gly--Asp peptides to alter .alpha..sub.v .beta..sub.3 integrin receptor-mediated binding of a cell such as an osteoclast, endothelial cell or smooth muscle cell to a matrix. The invention further provides methods for ameliorating the severity of a pathology characterized, in part, by an undesirable level of bone resorption, angiogenesis or restenosis in a subject.

Use of peptides for altering .alpha..sub.V .beta..sub.3 -mediated binding

The present invention provides Arg-Gly-Asp peptides that can reduce or inhibit the binding of osteoclasts to a matrix such as bone or can selectively alter integrin receptor binding. The invention also provides methods of using the Arg-Gly-Asp peptides to reduce or inhibit osteoclast binding to a matrix, to reduce or inhibit bone resorption in a subject and to alter .alpha..sub.V .beta..sub.3 binding.

Peptides for reducing or inhibiting bone resorption

Peptides useful for altering .alpha..sub.v .beta..sub.3 -mediated binding

The present invention provides a method of inhibiting an activity of a cell regulatory factor comprising contacting the cell regulatory factor with a purified polypeptide, wherein the polypeptide comprises a cell regulatory factor binding domain of a protein. The protein is characterized by a leucine-rich repeat of about 24 amino acids. In a specific embodiment, the present invention relates to the ability of decorin, a 40,000 dalton protein that usually carries a glycosaminoglycan chain, and more specifically to active fragments of decorin or its functional equivalents to bind TGF.beta.. The invention also provides a novel cell regulatory factor designated MRF. Also provided are methods of identifying, detecting and purifying cell regulatory factors and proteins which bind and affect the activity of cell regulatory factors.

Decorin fragments inhibiting cell regulatory factors

The present invention provides novel conjugates of a synthetic polypeptide containing RGD or (dR)GD and a biodegradable polymer, hyaluronate. The conjugates are prepared by any one of three different methods provided by the present invention: (1) an epoxide method (2) a sodium periodate method, and (3) a tresyl chloride method. The conjugates prepared by these methods are useful to aid in wound healing and tissue regeneration by providing a temporary matrix for tissue repair. The invention also provides novel RGD-peptides.

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San Diego, CA, United States of America

Daniel G Mullen