Fusion proteins comprising circularly permuted ligands

A fusion protein comprising a modified interleukin 2 (IL2) that is a modification of an original IL2 having amino acid residues numbered sequentially 1 through J with an amino terminus at residue 1 and a carboxyl terminus at residue J, said fusion protein having the following formula:

• (T.sup.1).sub.a --(S.sup.1).sub.b --X.sup.1 --(L).sub.c --X.sup.2 --(S.sup.2).sub.d --(T.sup.2).sub.e
• in which:
• X.sup.1 is a peptide consisting of an amino acid sequence having the sequence of residues n+1 through J of said original IL2;
• L is a linker;
• X.sup.2 is a peptide consisting of an amino acid sequence having the sequence of residues 1 through n of said original IL2;
• S.sup.1 and S.sup.2 are peptide spacers;
• n is an integer ranging from 1 to J-1;
• b, c, and d are each independently 0 or 1;
• a and e are each either 0 or 1, provided that a and e cannot both be 0;
• and
• T.sup.1 and T.sup.2 are cytotoxins.

A fusion protein comprising a modified granulocyte macrophage colony stimulating factor (GM-CSF) that is a modification of an original GM-CSF having amino acid residues numbered sequentially 1 through J with an amino terminus at residue 1 and a carboxyl terminus at residue J, said fusion protein having the following formula:

• (T.sup.1).sub.a --(S.sup.1).sub.b --X.sup.1 --(L).sub.c --X.sup.2 --(S.sup.2).sub.d --(T.sup.2).sub.e
• in which:
• X.sup.1 is a peptide consisting of an amino acid sequence having the sequence of residues n+1 through J of said original GM-CSF;
• L is a linker;
• X.sup.2 is a peptide consisting of an amino acid sequence having the sequence of residues 1 through n of said original GM-CSF;
• S.sup.1 and S.sup.2 are peptide spacers;
• n is an integer ranging from 1 to J-1;
• b, c, and d are each independently 0 or 1;
• a and e are each either 0 or 1, provided that a and e cannot both be 0;
• and
• T.sup.1 and T.sup.2 are cytotoxins.

A fusion protein comprising a modified granulocyte colony stimulating factor (G-CSF) that is a modification of an original G-CSF having amino acid residues numbered sequentially 1 through J with an amino terminus at residue 1 and a carboxyl terminus at residue J, said fusion protein having the following formula:

• (T.sup.1).sub.a --(S.sup.1).sub.b --X.sup.1 --(L).sub.c --X.sup.2 --(S.sup.2).sub.d --(T.sup.2).sub.e
• in which:
• X.sup.1 is a peptide consisting of an amino acid sequence having the sequence of residues n+1 through J of said original G-CSF;
• L is a linker;
• X.sup.2 is a peptide consisting of an amino acid sequence having the sequence of residues 1 through n of said original G-CSF;
• S.sup.1 and S.sup.2 are peptide spacers;
• n is an integer ranging from 1 to J-1;
• b, c, and d are each independently 0 or 1;
• a and e are each either 0 or 1, provided that a and e cannot both be 0;
• and
• T.sup.1 and T.sup.2 are cytotoxins.