Riso National Laboratory

Dako A/s

Pence, Inc.

Cancerforskningsfonden Af 1989 (fonden Til Fremme Af Exsperimentel Cancerforskning)

Arne Holm

Rolf Henrik Berg

Robert B Merrifield

James P Tam

Kristoffer Almdal

Walther B Pedersen

Robert S Hodges

Randall Thomas Irvin

Wah Yau Wong

Michael Ploug

Hasmukh B Sheth

Devon L Husband

Marianne Jartved Mathiesen

S&oslash;ren &Oslash;stergaard

Keld Danø

Ross Stephens

Claus Holst-Hansen

Søren Østergaard

A novel set of inhibitors of the binding interaction between human urokinase plasminogen activator (uPA) and its cell surface receptor (uPAR) has been developed. The inhibitors comprise of peptide fragments, monomeric or in multiple copies attached to a common scaffold, in which the amino acid sequence may include uncommon substituted amino acids to partially comprise of peptoid sequences. The present invention also relates to the use of such peptides in therapy, in particular for the treatment of cancer, having developed a modified non-human mammalian receptor to which the novel inhibitors are antagonistic.

Peptide antagonists of the human urokinase receptor and method for selecting them

A diagnostic method is disclosed which utilizes short C-terminal fragments of sensu lato derived protein OspC. The 4 amino-terminal acids Pro-Lys-Pro (SEQ ID NO: 22) are shown to be essential in immune reactivity between sera from patients suffering from early borreliosis and various OspC derivatives and it is shown that in order to be effective as a diagnostic agent, 5 consecutive amino acid residues long homologue of a fragment identical to the 10 C-terminal amino acids of OspC (SEQ DI NO: 1). Also disclosed are vaccines utilizing the short peptides as well as methods for their preparation.

Osp-C derived peptide fragments

A combinatorial library composition and method for using the library to construct oligomers effective to bind to a selected ligand is disclosed. The library composition includes at least two sets of ar oligomer libraries, each library set having selected oligomer subunit positions filled by known subunits, and other subunit positions containing permutations of subunits. In the selection method, oligomers from each library set are identified, and a new permutation library formed of subunits corresponding to the highest binding affinity oligomers in each library is screened for binding affinity to the selected ligand.

Combinational library composition and method

A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion. Preferred embodiments of a solid support for performing the synthesis are prepared from thin polyethylene sheet or film which has been grafted with polystyrene chains in a radical-initiated process in which the polyethylene sheet or film is immersed in a solution of optionally substituted styrene monomer in an alcohol such as methanol, the volume percentage of styrene in the solution preferably being about 30% v/v, and subjected to gamma irradiation.

Peptide synthesis method and solid support for use in the method

A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid-support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion. Preferred embodiments of a solid support for performing the synthesis are prepared from thin polyethylene sheet or film which has been grafted with polystyrene chains in a radical-initiated process in which the polyethylene sheet or film is immersed in a solution of optionally substituted styrene monomer in an alcohol such as methanol, the volume percentage of styrene in the solution preferably being about 30% v/v, and subjected to gamma irradiation.

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Holte, Denmark

Arne Holm