Inhibiting furin with polybasic peptides

US7033991B2 · kind B2 · utility

Assignee

• BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE · US

Inventors

• Iris Lindberg · New Orleans, US
• Angus Cameron · Bristol, GB
• Jon R. Appel · Irvine, US
• Richard A. Houghten · Del Mar, US

Key dates

• Filing date: Jul 16, 2001
• Grant date: Apr 25, 2006
• Expiry date: Jul 16, 2021

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/07
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Small, polybasic peptides are disclosed that are effective as furin inhibitors, e.g. hexa- to nona-peptides having L-Arg or L-Lys in most positions. Removing the peptide terminating groups can improve inhibition of furin. High inhibition was seen in a series of non-amidated and non-acetylated polyarginines. The most potent inhibitor identified to date, nona-L-arginine, had a Ki against furin of 40 nM. Non-acetylated, poly-D-arginine-derived molecules are preferred furin inhibitors for therapeutic uses, such as inhibiting certain bacterial infections, viral infections, and cancers. Due to their relatively small size, these peptides should be non-immunogenic. These peptides are efficiently transported across cell membranes.