title: A new phage-display tumor-homing peptide fused to antiangiogenic peptide generates a novel bioactive molecule with antimelanoma activity.
abstract: Phage-display peptide libraries have been widely used to identify specific peptides targeting in vivo tumor cells and the tumor vasculature and playing an important role in the discovery of antitumor bioactive peptides. In the present work, we identified a new melanoma-homing peptide, (-CVNHPAFAC-), using a C7C phage-display library directed to the developing tumor in syngeneic mice. Phage were able to preferentially target melanoma in vivo, with an affinity about 50-fold greater than that with normal tissue, and the respective synthesized peptide displaced the corresponding phage from the tumor. A preferential binding to endothelial cells rather than to melanoma cells was seen in cell ELISA, suggesting that the peptide is directed to the melanoma vasculature. Furthermore, the peptide was able to bind to human sonic hedgehog, a protein involved in the development of many types of human cancers. Using a new peptide approach therapy, we coupled the cyclic peptide to another peptide, HTMYYHHYQHHL-NH(2), a known antagonist of VEGFR-2 receptor, using the GYG linker. The full peptide CVNHPAFACGYGHTMYYHHYQHHL-NH(2) was effective in delaying tumor growth (P < 0.05) and increasing animal survival when injected systemically, whereas a scramble-homing peptide containing the same antagonist did not have any effect. This is the first report on the synthesis of a tumor-homing peptide coupled to antiangiogenic peptide as a new anticancer therapeutics.
authors: UNONEX, Department of Microbiology, Immunology, and Parasitology, Universidade Federal de São Paulo, Rua Botucatu 862, 8th floor, Sao Paulo 04023, SP, Brazil. almatsuo@unifesp.br
authors: Alisson L
authors: AL
authors: Matsuo
authors: Maria A
authors: MA
authors: Juliano
authors: Carlos R
authors: CR
authors: Figueiredo
authors: Wagner L
authors: WL
authors: Batista
authors: Aparecida S
authors: AS
authors: Tanaka
authors: Luiz R
authors: LR
authors: Travassos
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D020533:Angiogenesis Inhibitors; D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins