主权项 |
1. A method of treating or ameliorating tissue damage in a subject in need thereof, said tissue damage resulting from a disease or condition, wherein said method comprises intravenously administering a composition comprising an isolated mutant form of stromal cell derived factor-1 (SDF-1) peptide comprising the formula of a mutant SDF-1 (mSDF-1), mSDF-1-Yz, Xp-mSDF-1, or Xp-mSDF-1-Yz, wherein said SDF-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:(SEQ ID NO: 53)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 VC I D P K L K W I Q E Y L E K A L N K,wherein X3, X4, X5, and X6 are any amino acid, 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) Yz is a proteinogenic amino acid(s) or protease protective organic group and z is any integer from 1 to 4; c) said mSDF-1 or said mSDF-1-Yz 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; and d) said Xp-mSDF-1 or said Xp-mSDF-1-Yz 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; wherein said isolated mutant form of SDF-1 is administered intravenously in an amount sufficient to treat or ameliorate said tissue damage in said subject. |