%0 Journal Article %A Motohiro Nonaka %A Hideaki Mabashi-Asazuma %A Donald L. Jarvis %A Kazuhiko Yamasaki %A Tomoya O. Akama %A Masato Nagaoka %A Toshio Sasai %A Itsuko Kimura-Takagi %A Yoichi Suwa %A Takashi Yaegashi %A Chun-Ten Huang %A Chizuko Nishizawa-Harada %A Michiko N. Fukuda %T Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides %D 2020 %R 10.1101/2020.10.12.335851 %J bioRxiv %P 2020.10.12.335851 %X IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminal domain, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide representing the Anxa1 N-terminus as target. Peptide sequences were identified, synthesized as D-amino acids, and designated as dTIT7, which was shown to bind the ANXA1 N-terminus. Whole body imaging of mouse brain tumors modeled with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered geldanamycin (GA)-conjugated dTIT7 suppressed brain tumor growth. Ours is a proof-of-concept experiment showing that Anxa1-binding D-peptide could be developed as an orally-administrable, tumor vasculature-targeted therapeutic.Role of each author: MN designed and performed experiments, analyzed data, and wrote the manuscript; HMA and DLJ produced recombinant ANXA1 protein; KY conducted NMR analysis and data analysis; TOA designed, performed and analyzed LC-MS/MS data; MN, TS, IKT, YS, and TY analyzed peptide-binding assays and performed in silico structural analysis; CTU produced lentivirus for luciferase expression; CNH performed peptide binding assays, tissue culture and animal experiments; and MNF supervised the project and wrote the manuscript. %U https://www.biorxiv.org/content/biorxiv/early/2020/10/12/2020.10.12.335851.full.pdf