Inhibition of Melittin Activity Using a Small Molecule with an Indole Ring

Sayuki Kanemitsu, Kenta Morita, Yudai Tominaga, Kanon Nishimura, Tomoko Yashiro, Haruka Sakurai, Yumemi Yamamoto, Ikuo Kurisaki, Shigenori Tanaka, Masaki Matsui, Tooru Ooya, Atsuo Tamura, Tatsuo Maruyama*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated d-amino acids as potential inhibitors targeting l-peptide toxins. Among the l- and d-amino acids tested, we found that d-tryptophan (d-Trp) acted as an inhibitor of melittin-induced hemolysis. We then evaluated various Trp derivatives and found that 5-chlorotryptamine (5CT) had the largest inhibitory effect on melittin. The indole ring, amino group, and steric hindrance of an inhibitor played important roles in the inhibition of melittin activity. Despite the small size and simple molecular structure of 5CT, its IC50was approximately 13 μg/mL. Fluorescence quenching, circular dichroism measurements, and size-exclusion chromatography revealed that 5CT interacted with Trp19 in melittin and affected the formation of the melittin tetramer involved in hemolysis. Molecular dynamics simulation of melittin also indicated that the interaction of 5CT with Trp19 in melittin affected the formation of the tetramer.

Original languageEnglish
Pages (from-to)5793-5802
Number of pages10
JournalJournal of Physical Chemistry B
Volume126
Issue number31
DOIs
Publication statusPublished - 2022 Aug 11
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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