PROTEASE RESISTANT MUTANTS OF STROMAL CELL DERIVED FACTOR-1 IN THE REPAIR OF TISSUE DAMAGE

摘要

Disclosed is an isolated mutant stromal cell derived factor-1 (SDF-1) peptide comprising the formula of mSDF-1 or Xp-mSDF-1, wherein said SDF-1 is a peptide comprising the amino acid sequence of at least amino acids 1-8 of SEQ ID NO:52 and which is optionally extended at the C terminus by all or any portion of the remaining sequence of SEQ ID NO:52, shown as amino acids 9-68, and wherein: e) X is a proteinogenic amino acid or a protease protective organic group; p is an integer between 1 and 4; mSDF-1 is a mutant form of said SDF-1 comprising a mutation of the fourth or the fourth and the fifth amino acid from the N terminus of said SDF-1, wherein mSDF-1 has chemoattractant activity for T cells and is inactivated by matrix metalloproteinase-2 (MMP-2) at a rate that is less than one-half of the rate at which native SDF-1 peptide is inactivated; and h) Xp-mSDF-1 is a mutant form of said SDF-1 comprising a mutation of the fourth and/or the fifth amino acid from the N terminus of said SDF-1, wherein Xp-mSDF-1 has chemoattractant activity for T cells, is inactivated by dipeptidyl peptidase IV (DPPIV) at a rate that is less than one-half of the rate at which native SDF-1 is inactivated, and is inactivated by MMP-2 at a rate that is less than one-half of the rate at which native SDF-1 is inactivated.