Institut Pasteur

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Benoit Marteyn

Françoise Baleux

Yves-Marie Coic

Philippe J Sansonetti

The invention relates to a peptidomimetic comprising or consisting of a D amino-acid sequence having at least 75% identity with SEQ ID NO: 1 or SEQ ID NO: 2, or variants or fragments thereof, in particular a peptidomimetic having the capability to interact at least with: neutrophils and/or neutrophil granules, and/or lactoferrin, and/or globet-cells and/or Muc2 proteins, and/or mucus and/or airway sputum. The peptidomimetic may have the capacity to adopt a multimeric, especially a trimeric, organization, and can be labelled, or associated with a reporter or a carrier entity, or associated with an active molecule. The invention also relates to a Solid-Phase Synthesis method for synthesizing a peptidomimetic of the invention, compositions comprising the same and use of the peptidomimetics as a medicamentor an inflammation marker or a neutrophilic inflammation marker. The invention also relates to the use of a peptidomimetic as a probe or marker for staining purposes, or to detect mucus production, or neutrophils, or to detect or monitor diseases or conditions, especially neutrophilic inflammation. The invention also relates to the use of a polypeptide comprising or consisting of SEQ ID NO: 3, or variants or fragments thereof, as probe or marker for staining lactoferrin, in particular neutrophil lactoferrin, or a probe or marker for investigating neutrophilic inflammation, especially in an imaging method.

Peptidomimetics, method of synthesis and uses thereof

The invention relates to polypeptides, defined through a consensus sequence, having a length from 10 to 80 amino-acid residues, and whose polypeptidic sequence comprises or consists of the consensus sequence P1(X)P3(X)P5(X)P6(X)P7 (SEQ ID NO: 1), presenting specific patterns. The polypeptides of the invention target glycosylated Muc2 proteins. The invention also relates to methods of synthesis of such polypeptides, to their nucleic acids and uses thereof. The polypeptidic sequence of the polypeptides of the invention can be part of the N-terminal sequence of a mucus-binding (MUB) domain, especially a mucus-binding (MUB) domain of several species. The invention also relates to chimeric molecule(s) comprising such polypeptides, which are labelled, and vectors, especially plasmids and population of cells or composition comprising polypeptides of the invention. Synthesis methods encompass biotechnological or chemical production. Polypeptides of the invention can be used in staining experiments, as a probe or marker for staining Muc2 protein(s) contained in mucus layer(s), to detect in vitro mucus production or mucus composition in human colon or monitoring any one of the following disease conditions: neoplasic disease(s), including mucinous carcinoma(s), gastric cancer(s) or colorectal cancer(s), especially colon cancer(s), cystic fibrosis, intestine inflammatory disease(s) such as inflammatory bowel disease (IBD) and ulcerative colitis. The invention also relates to a method for manufacturing a medicament. In a particular embodiment, use of polypeptides of the invention can be made for marking neutrophiles.

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Paris, France

Benoit Marteyn