Basic peptides and pharmaceutical compositions containing same

A NST300 compound of the general formula Ia comprising the following components:

• X1—X2[(X3)a/(X4)b/(X5)c]—X6
• wherein:
• X1 stands for a saturated or unsaturated fatty acid residue comprising 6-20 carbon atoms;
• or a cysteine residue bound through a thioether bond to a prenyl group comprising 5-20 carbon atoms;
• said residue being linked to the adjacent component of the compound through an amide bond;
• X2 is selected among 0-3 glycine residues and 0-2 β-amino alanine molecules;
• X3 comprises 1-6 amino acids, of which 1-6 are positively charged, the other amino acid residues being polar uncharged amino acids;
• X4 comprises 1-6 amino acids, of which 1-2 are aromatic amino acids, the other amino acids being selected among polar uncharged amino acids and hydrophobic amino acids;
• X5 is a compound of general formula II
• wherein Z stands for a spacer group selected among an alkane containing 1-4 carbon atoms and an alkene containing 2-4 carbon atoms, J stands for a functional group selected among amines, thiols, alcohols, carboxylic acids, esters, aldehydes and alkyl halides;
• U is a labeling group;
• and
• X6 being 0 or a saturated or unsaturated fatty acid residue comprising 6-20 carbon atoms;
• or a cysteine residue bound through a thioether bond to a prenyl group comprising 5-20 carbon atoms;
• wherein:
• a stands for an integer of 1-8;
• b stands for an integer of 1-8;
• the groups X3 and X4 being located at various places in the compound;
• c stands for 0-10;
• such that within the subunit [(X3)a/(X4)b/(X5)c]
• (X3)a comprises at least 6 positively charged amino acids and the groups X3, X4 and X5 being located at various places, wherein U is a labeling group for specific binding selected among biotin and a group containing a substituent selected among a fluorescein, a radioisotope and a paramagnetic contrast agent.

A method for selectively targeting a medicinally-useful agent to cells that have undergone CMLA loss, within a region of mammalian subject, comprising administering to said cells said medicinally-useful agent wherein said agent comprises the compound of formula I, said compound comprising the following components:

• X1—[(X3)a/(X4)b]:
• wherein:
• X1 stands for a saturated or unsaturated fatty acid residue comprising 6-20 carbon atoms;
• or a cysteine residue bound through a thioether bond to a prenyl group comprising 5-20 carbon atoms;
• said residue being linked to the adjacent component of the compound through an amide bond;
• X3 comprises 1-6 amino acids, of which 1-6 are positively charged, the other amino acid residues being polar uncharged amino acids;
• and
• X4 comprises 1-6 amino acids, of which 1-2 are aromatic amino acids, the other amino acids being selected among polar uncharged amino acids and hydrophobic amino acids;
• wherein:
• a stands for an integer of 1-8;
• b stands for an integer of 1-8;
• and
• (X3)a comprises at least 6 positively charged amino acids and the groups X3 and X4 being located at various places in the compound, wherein the compound is capable of binding to a cell membrane having a loss of cell membrane lipid asymmetry (CLMA).