Anti-Angiogenesis Activities of Novel Peptide Complexes: Mitochondria-Disruptive 9mer Peptides Conjugated with the Integrin alpha V beta 3-Homing Cyclic RGD Motif

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  • IWASAKI Takashi
    Faculty of Agriculture, Tottori University Faculty of Agriculture, Tottori University
  • YAMAKAWA Minoru
    Insect Mimetics Research Unit, National Institute of Agrobiological Sciences Insect Mimetics Research Unit, National Institute of Agrobiological Sciences
  • ASAOKA Ai
    Insect Mimetics Research Unit, National Institute of Agrobiological Sciences Insect Mimetics Research Unit, National Institute of Agrobiological Sciences
  • KAWANO Tsuyoshi
    Faculty of Agriculture, Tottori University Faculty of Agriculture, Tottori University
  • ISHIBASHI Jun
    Insect Mimetics Research Unit, National Institute of Agrobiological Sciences Insect Mimetics Research Unit, National Institute of Agrobiological Sciences

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Abstract

RGD peptides are popular drug delivery tools in treating integrin αVβ3-expressing malignant tumors and tumor vasculature cells. We investigated the specific delivery and pharmacological potential of enantiomeric mitochondria-disruptive peptides (RLYLRIGRR-NH2, RLRLRIGRR-NH2, ALYLAIRRR-NH2, and RLLLRIGRR-NH2) after conjugation with an integrin αVβ3-homing peptide, cyclic pentameric RGD peptide. The cyclic RGD-conjugated mitochondria-disruptive peptides exhibited specific internalization, apoptosis induction, and cytotoxicity against integrin αVβ3-high-expressing human umbilical vein endothelial cells. Our findings indicate that these novel peptide complexes might prove good anti-angiogenesis reagents.

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