Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin-Targeting Thiazole Analogue of Bisebromoamide

Heather J Johnston, Sarah K Boys, Ashraff Makda, Neil O Carragher, Alison Nicola Hulme

Research output: Contribution to journalArticlepeer-review

Abstract

Systematic alanine-scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, is enabled by targeting the solid phase peptide synthesis of thiazole analogues. The synthetic Tz-BBA analogues have comparable cytotoxicity (nM) to bisebromoamide and cellular morphology assays indicate that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT-116) cells has been explored using reverse phase protein array (RPPA) analysis, which shows a dose-dependent response of IRS-1 expression. Alanine-scanning reveals a structural dependence to the cytotoxicity, actin-targeting and pathway inhibition, and allows a new readily-synthesised lead to be proposed.
Original languageEnglish
Pages (from-to)1621-1627
Number of pages7
JournalChemBioChem
Volume17
Issue number17
Early online date15 Jun 2016
DOIs
Publication statusPublished - 5 Aug 2016

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