title: Anti-angiogenesis activities of novel peptide complexes: mitochondria-disruptive 9mer peptides conjugated with the integrin alpha V beta 3-homing cyclic RGD motif.
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-NH(2), RLRLRIGRR-NH(2), ALYLAIRRR-NH(2), and RLLLRIGRR-NH(2)) 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.
authors.affiliation: Faculty of Agriculture, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Yamakawa
authors.forename: Ai
authors.initials: A
authors.lastname: Asaoka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kawano
authors.forename: Jun
authors.initials: J
authors.lastname: Ishibashi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D010456:Peptides, Cyclic / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D020533:Angiogenesis Inhibitors; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide