Protease-resistant mutants of stromal cell derived factor-1 in the repair of tissue damage

An isolated mutant form of stromal cell derived factor-1 (SDF-1) peptide comprising the formula of a mutant SDF-1 (mSDF-1) or Xp-mSDF-1, wherein said mSDF-1 is a peptide comprising the amino acid sequence of at least amino acids 1-8 of SEQ ID NO:53 and which is optionally extended at the C-terminus by all or any portion of the remaining sequence of SEQ ID NO:53, said SEQ ID NO:53 comprising the amino acid sequence:

• K P X3 X4 X5 X6 Y R C P C R F F E S H V A R A N V K H L K I L N T P N C A L Q I V A R L K N N N R Q V C I D P K L K W I Q E Y L E K A L N K (SEQ ID NO:53), wherein
• X3 is any amino acid;
• X4 is serine or valine;
• X5 is leucine, proline, threonine, or valine;
• and
• X6 is any amino acid residue,
• and wherein
• a) Xp is a proteinogenic amino acid(s) or a protease protective organic group and p is any integer from 1 to 4;
• b) said mSDF-1 maintains chemoattractant activity for T cells and is inactivated by matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), leukocyte elastase, and/or cathepsin G at a rate that is at least 50% less than the rate of inactivation of native SDF-1;
• c) said Xp-mSDF-1 maintains chemoattractant activity for T cells, is inactivated by dipeptidyl peptidase IV (DPPIV) at a rate that is at least 50% less than the rate at which native SDF-1 is inactivated, and is inactivated by MMP-2, MMP-9, leukocyte elastase, and/or cathepsin G at a rate that is at least 50% less than the rate of inactivation of native SDF-1;
• and
• d) said SDF-1 peptide does not comprise the amino acid sequence of at least amino acids 1-8 of SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, or SEQ ID NOs:65-67.