Design of Peptide Inhibitors for the Importin α/β Nuclear Import Pathway by Activity-Based Profiling

Shunichi Kosugi, Masako Hasebe, Tetsuyuki Entani, Seiji Takayama, Masaru Tomita, Hiroshi Yanagawa

Research output: Contribution to journalArticlepeer-review

170 Citations (Scopus)


Despite the current availability of selective inhibitors for the classical nuclear export pathway, no inhibitor for the classical nuclear import pathway has been developed. Here we describe the development of specific inhibitors for the importin α/β pathway using a novel method of peptide inhibitor design. An activity-based profile was created via systematic mutational analysis of a peptide template of a nuclear localization signal. An additivity-based design using the activity-based profile generated two peptides with affinities for importin α that were approximately 5 million times higher than that of the starting template sequence. The high affinity of these peptides resulted in specific inhibition of the importin α/β pathway. These peptide inhibitors provide a useful tool for studying nuclear import events. Moreover, our inhibitor design method should enable the development of potent inhibitors from a peptide seed.

Original languageEnglish
Pages (from-to)940-949
Number of pages10
JournalChemistry and Biology
Issue number9
Publication statusPublished - 2008 Sept 22



ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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