Development of oligoarginine-drug conjugates linked to new peptidic self-cleavable spacers toward effective intestinal absorption

Yoshio Hayashi; Kentaro Takayama; Yuka Suehisa; Takuya Fujita; Jeffrey-Tri Nguyen; Shiroh Futaki; Akira Yamamoto; Yoshiaki Kiso

doi:10.1016/j.bmcl.2007.07.004

Development of oligoarginine-drug conjugates linked to new peptidic self-cleavable spacers toward effective intestinal absorption

Bioorg Med Chem Lett. 2007 Sep 15;17(18):5129-32. doi: 10.1016/j.bmcl.2007.07.004. Epub 2007 Jul 7.

Authors

Yoshio Hayashi¹, Kentaro Takayama, Yuka Suehisa, Takuya Fujita, Jeffrey-Tri Nguyen, Shiroh Futaki, Akira Yamamoto, Yoshiaki Kiso

Affiliation

¹ Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan. yhayashi@ps.toyaku.ac.jp

PMID: 17662604
DOI: 10.1016/j.bmcl.2007.07.004

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arginine / chemistry*
Arginine / pharmacology
Chromatography, High Pressure Liquid
Intestinal Absorption / drug effects*
Oligopeptides / chemistry*
Oligopeptides / pharmacology

Substances

Oligopeptides
Arginine