Solubilizing hydrophobic peptides, useful e.g. in vaccines against infectious microbes or tumors, by attachment of at least three arginine or lysine residues

摘要

Solubilizing, or improving solubility of, a peptide (I) in aqueous medium comprising covalent attachment of at least 3 residues of Arg and/or Lys, provided at least one is Arg, in L or D form, distributed over the N and/or C termini in the form of a linear or branched chain, is new. Independent claims are also included for: (1) peptide ligand (Ia) of MHC (major histocompatibility complex) modified by attachment of at least 3 residues of Arg and/or Lys, provided at least one is Arg, in L or D form, distributed over the N and/or C termini in the form of a linear or branched chain; and (2) vaccine containing at least one peptide that contains at least one hydrophobic epitope derived from an antigenic protein of a microbial pathogen or tumor and modified by the new method or is (Ia). ACTIVITY : Virucide; Antibacterial; Parasiticide; Fungicide; Cytostatic. The modified melanoma Melan/Mart-1 peptide (4R-ELA) of sequence (Arg)4-Glu-Leu-Ala-Gly-Ile-Gly-Ile-Leu-Thr-Val was administered (50 Microg plus 300 Microg of the P40 adjuvant) subcutaneously to mice. Ten days later, spleen cells were recovered and cultured in presence of interleukin-2 and of fixed antigen-presenting cells loaded with ELA. The effector cells were restimulated after 7 days, then after a further 5 days they were tested in a chromium release assay against EL4 A2/kb cells loaded with peptide. At an effector:target ratio 100, the specific lysis was over 80%. MECHANISM OF ACTION : Vaccine; Gene Therapy.