Agence Nationale De Valorisation De La Recherche (anvar)

Monique Parant

Louis A Chedid

Pierre Lefrancier

Jean Choay

Edgar Lederer

Francoise Marguerite Audibert

Edgar Sache

Michael Sela

Michel Level

Nigel Phillips

Francine Parant

Jean-Marie Bernard

The invention relates to muramyleptide derivatives resulting essentially from the conjugation or the coupling, as the case may require, through an arm, between a muramylpeptide and a group containing two atoms contiguous with one another to each of which is attached a lipophile chain comprising from 8 to 100 carbon atoms, preferably from 14 to 24 carbon atoms. The derivatives according to the invention are endowed with remarkable stimulating properties with respect to the activation of macrophages, of which they amplify the tumoricidal properties.

Lipophile derivatives of muramylpeptides having properties of activating

The compounds have the structure 2-(2-amino or alkyl-amido-2-desoxy-3-O-D-glucopyranosyl)-alkanyl-dipeptide, possibly substituted on the saccharide residue the amino acid residue at the end of the peptide chain being a D-glutamyl residue whose .alpha.-carboxy function is esterified and .gamma.-carboxyl function amidated. The compounds are valuable as immunological medicaments.

Novel compounds of the muramyl peptide

The novel products are water-soluble oligomers, free of N-acetyl-glucosamine units, and of which the monomer elements include a group derived from muramic acid on which is fixed a chain of the peptide type including at least two aminoacyl residues, the first being selected from among: L-alanyl, L-arginyl, L-asparagyl, L-histidyl, L-hydroxyprolyl, L-isoleucyl, L-leucyl, L-methionyl, L-phenylalanyl, L-prolyl, L-seryl, L-threonyl, L-tryptophanyl, L-valyl, and the second aminoacyl is D-glutamyl or D-isoglutaminyl. They are useful for their immunoregulator properties and for the preparation of pharmaceutical compositions.

Oligomers of compounds of the muramyl-peptide type and medicaments

A polymer of peptidic type formed by a chain formed from aminoacyl residues preferably derived of at least one of the amino-acid residues selected from the class consisting of .alpha.,.gamma.-diaminobutyric acid, ornithine, lysine, homo-lysine, of which the lateral amino functions portionally carry peptide branches of which the aminoacyl residues are preferably derived of those selected from the class consisting of alanine, glycine, .alpha.-aminobutyric acid, valine, leucine and proline, the above-said peptide polymer having an average molecular weight comprised between about 50,000 and 250,000, and to which are bound covalently, muramyl-peptide units of which the two first aminoacid residues bound to the muramyl group are stereoisomers of the D series, the second aminoacid residue having the structure of the glutamic acid. This product is useful as anti-infectious agent.

Muramyl-peptides fixed to peptide-polymers and pharmaceutical

The invention relates to new compounds useful notably as regulator of immune responses and which are derivatives of muramyl peptides substituted at the end of the peptide chain by a group containing at least four carbon atoms.

Muramyl peptide derivatives and pharmaceutical compositions

The invention relates to a new method for increasing the resistance of the organism to pathogenic germs and to compositions to carry out said method. In this method, one administers an effective dose of N-acetyl-muramyl-L-alanyl-D-isoglutamine or analogs responding to the formula ##STR1## wherein R.sub.1 is OH or NH.sub.2, R.sub.2 is OH, NH.sub.2 or a peptidic residue containing from 1 to 6 aminoacids, with the proviso that R.sub.1 and R.sub.2 are not simultaneously NH.sub.2.

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Paris, France

Monique Parant