Development of oligoarginine-drug conjugates linked to new peptidic self-cleavable spacers toward effective intestinal absorption.
We designed and synthesized new peptidic self-cleavable spacers that released a parent drug via succinimide formation and the oligoarginine-based cargo-transporter (OACT) system. The self-cleavable efficacy of these compounds was studied and the conversion time was controlled by an amino acid side-chain structure next to the succinyl moiety on the spacer. These novel self-cleavable spacers are promising for developments of the OACT system as means to potentially enhance intestinal absorption of parent drugs.
Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan. yhayashi@ps.toyaku.ac.jp
Yoshio
Y
Hayashi
Kentaro
K
Takayama
Yuka
Y
Suehisa
Takuya
T
Fujita
Jeffrey-Tri
JT
Nguyen
Shiroh
S
Futaki
Akira
A
Yamamoto
Yoshiaki
Y
Kiso
D001120:Arginine / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D007408:Intestinal Absorption / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology
D009842:Oligopeptides; D001120:Arginine