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Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides

PLoS ONE. 2021-01; 
Motohiro Nonaka , Hideaki Mabashi-Asazuma , Donald L Jarvis , Kazuhiko Yamasaki , Tomoya O Akama , Masato Nagaoka , Toshio Sasai , Itsuko Kimura-Takagi , Yoichi Suwa , Takashi Yaegashi , Chun-Teng Huang , Chizuko Nishizawa-Harada , Michiko N Fukuda
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Peptide Synthesis , dSPT7 (SPTSLLF), dLKG7 (LKGMLRI) and dLLS7 (LLSWPSA), were synthesized by GenScript (Piscataway, NJ). Get A Quote

摘要

We previously reported that IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminus, 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. We then identified peptide sequences, synthesized them as D-amino acids, and designated the resulting peptide dTIT7, which we showed bound to the ANXA1 N-terminus. Whole body imaging of mouse brain tumor models injected with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered dTIT7/geldanamycin (GA) co... More

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