Rational hopping of a peptidic scaffold into non-peptidic scaffolds: structurally novel potent proteasome inhibitors derived from a natural product, belactosin A

Shuhei Kawamura; Yuka Unno; Takatsugu Hirokawa; Akira Asai; Mitsuhiro Arisawa; Satoshi Shuto

doi:10.1039/c3cc48818g

Rational hopping of a peptidic scaffold into non-peptidic scaffolds: structurally novel potent proteasome inhibitors derived from a natural product, belactosin A

Chem Commun (Camb). 2014 Mar 7;50(19):2445-7. doi: 10.1039/c3cc48818g. Epub 2014 Jan 22.

Authors

Shuhei Kawamura¹, Yuka Unno, Takatsugu Hirokawa, Akira Asai, Mitsuhiro Arisawa, Satoshi Shuto

Affiliation

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. shu@pharm.hokudai.ac.jp.

PMID: 24452398
DOI: 10.1039/c3cc48818g

Abstract

Rational scaffold hopping of a natural product belactosin A derivative was successfully achieved based on the pharmacophore model constructed. The peptidic scaffold was replaced by significantly simplified non-peptidic scaffolds, by which weak belactosin A (IC50 = 1440 nM) was converted into highly potent non-peptidic inhibitors (IC50 = 26-393 nM).

Publication types

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

MeSH terms

Biological Products / chemistry*
Cell Survival / drug effects
HCT116 Cells
Humans
Intercellular Signaling Peptides and Proteins
Peptides / chemistry*
Proteasome Inhibitors / chemistry*
Proteasome Inhibitors / pharmacology

Substances

Biological Products
Intercellular Signaling Peptides and Proteins
Peptides
Proteasome Inhibitors
belactosin A