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.
Hayashi
Yoshio
Y
Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan. yhayashi@ps.toyaku.ac.jp
Takayama
Kentaro
K
Suehisa
Yuka
Y
Fujita
Takuya
T
Nguyen
Jeffrey-Tri
JT
Futaki
Shiroh
S
Yamamoto
Akira
A
Kiso
Yoshiaki
Y
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