Mallinckrodt Medical, Inc.

University of Michigan

Mallinckrodt, Inc.

Biosynthema Inc.

Leon R Lyle

Raghavan Rajagopalan

Steven L Kunkel

Robert M Strieter

Ananthachari Srinivasan

Karen F Deutsch

Thomas J Dunn

T Jeffrey Dunn

Alexander Lazarevich Klibanov

Kathleen M Miller

M Elizabeth Thomas

Stable analogs of cyclic peptides containing disulfide linkages are disclosed. The disulfide linkage is modified by one of four methods: (a) sulfide contraction, (b) isosteric substitution, (c) thioketal expansion, or (d) alkylation expansion. In sulfide contraction the disulfide bond (&mdash;S&mdash;S&mdash;) is replaced with a monosulfide bond (&mdash;S&mdash;) in which a bifunctional effector molecule, such as a ligand or chemotoxic agent, is bound to the new peptide linkage. In isosteric substitution, one sulfur atom is replaced with a carbon atom and at least one of the carbon atoms at the modified site is a bifunctional effector molecule. In thioketal expansion, an alkylidene unit (&mdash;CR C &mdash;) is inserted between the two sulfur atoms. In alkylation expansion, an alkyl moiety of from C to C , is inserted between the two sulfur atoms.

Stable analogs of bioactive peptides containing disulfide linkages

Selectively binding ultrasound contrast agents

A diagnostic composition suitable for administration to a warm-blooded animal comprising somatostatin or a molecule capable of interacting with the somatostatin receptor labeled with a radionuclide by means of a chelate ligand capable of administration to an animal to produce reliable visual imaging of tumors or therapeutic effects on tumors.

Radiolabelled peptide compounds

A method of imaging a target site in an animal's body in which a labelled chemokine is introduced into the animal's body and allowed to accumulate at a target site which includes corresponding receptor molecules. The accumulated, labelled chemokine material then is detected so as to image the target site of the body.

Radiolabeled neutrophil activating peptides for imaging

A composition suitable for administration to a warm-blooded animal comprising antisense MCP-1 peptide or oligonucleotide or a molecule capable of interacting with MCP-1 peptide or information for its synthesis which may or may not be labeled with a radionuclide by means of a chelate ligand capable of administration to an animal to produce reliable visual imaging of areas of potential restenosis or to produce therapeutic effects on areas of areas of potential restenosis.

Therapeutic treatment for inhibiting vascular restenosis

Ligands that are capable of forming metal complexes are incorporated directly into peptides at nonbiologically active locations. The metal complex serves as a bifunctional agent and as a spacer molecule. In one aspect of the invention, the ligands are prepared by replacing a nonbiologically active peptide spacer sequence with either Cys-Gly-Gly-Glu(.gamma.-)CO- (SEQ ID NO:1) or Cys-Gly-Gly-Lys(.epsilon.-)NH-CO(CH.sub.2).sub.2 -CO- (SEQ ID NO:2). In these examples, unnatural peptide bonds are used to attach the ligand to the terminal end of the peptide. Peptides incorporating such ligands are also disclosed. Other spacer ligands which may be incorporated into peptides include the following natural peptide sequences: -Cys-Gly-His-, -Asp-Gly-Cys-, -Glu-Gly-Cys-, -Gly-Asp-Cys-, and -Gly-Glu-Cys-. Unnatural tripeptides which function as spacer ligands include: -Cys-Gly-(imidazolyl glycyl)-, -isoCys-Gly-(imidazolyl glycyl)-, and -isoCys-Gly-His-. When the above peptide sequences are present in a nonbiologically active peptide spacer, they are able to form metal complexes with desired metal ions, and the resulting complexes serve as bifunctional agents and as spacer molecules in the peptide.

Metal chelates as spacer compounds in biologically active peptides

A method of imaging a target site in an animal's body in which a labelled CC chemokine or Monocyte Attractant Protein (MCP) material is introduced into the animal's body and allowed to accumulate at a target site which includes MCP receptor molecules. The accumulated, labelled MCP material is then detected so as to image the target site of the body.

Labelled monocyte chemoattractant protein material and medical uses

A diagnostic composition suitable for administration to a warm-blooded animal comprising hirudin or a molecule capable of interacting with the hirudin receptor labeled with a radionuclide by means of a chelate ligand capable of administration to an animal to produce reliable visual imaging of thrombus.

A method of imaging a target site in an animal's body in which a labelled CXC chemokine is introduced into the animal's body and allowed to accumulate at a target site which includes Interleukin-8 receptor molecules. The accumulated, labelled CXC chemokine is then detected so as to image the target site of the body.

Labelled interleukin-8 and medical uses thereof

A diagnostic composition suitable for administration to a warm-blooded animal comprising a whole, fragmented, or recombinant MH-1 monoclonal antibody labeled with a Tc-99m triamide thiolate (N.sub.3 S) bifunctional chelate capable of intravenous injection into an animal to produce reliable visual imaging of thrombi.

Growing community of inventors

Webster Groves, MO, United States of America

Leon R Lyle