Synthesis of VIP-Lipopeptide Using a New Linker to Modify Liposomes: Towards the Development of a Drug Delivery System for Active Targeting

• Published in: Chemical & pharmaceutical bulletin Vol. 61; no. 11; pp. 1184 - 1187
• Main Authors: Masaka, Toru, Matsuda, Takuya, Li, Yingpeng, Koide, Yuki, Takami, Akira, Yano, Kenji, Imai, Ryosuke, Ichihara, Risa, Yagi, Nobuhiro, Suzuki, Hideharu, Hikawa, Hidemasa, Terada, Katsuhide, Yokoyama, Yuusaku
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.11.2013; Pharmaceutical Society of Japan; Pharmaceutical Soc Japan
• Subjects: Acetates - chemistry; Alkylation; Carbonates - chemistry; Cesium - chemistry; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Dioxolanes - chemical synthesis; Dioxolanes - chemistry; Drug Carriers - chemistry; drug delivery system; isopropylidene-D-threitol; Life Sciences & Biomedicine; linker; lipopeptide; Liposomes - chemistry; peptide synthesizer; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Solid-Phase Synthesis Techniques; Vasoactive Intestinal Peptide - chemical synthesis; Vasoactive Intestinal Peptide - chemistry; linker; isopropylidene-D-threitol; lipopeptide; CONJUGATE; drug delivery system; LIGAND; peptide synthesizer; PEPTIDE
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c13-00518

A new component for the solid phase peptide synthesis of lipopeptide, 2-[(4R,5R)-5-({[(9H-fluoren-9-yl)methoxy]carbonylaminomethyl}-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]acetic acid (2), was designed and synthesized from (−)-2,3-O-isopropylidene- D -threitol (3) in 4 steps. The key step was the selective alkylation of 3 with benzyl bromoacetate in the presence of Cs2CO3. Vasoactive intestinal peptide (VIP)-lipopeptide (1) incorporating this linker was synthesized by solid phase peptide synthesis.