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

Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid‐phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they...

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Autores principales: Johnston, Heather J., Boys, Sarah K., Makda, Ashraff, Carragher, Neil O., Hulme, Alison N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Full Papers
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096027/
https://www.ncbi.nlm.nih.gov/pubmed/27304907
http://dx.doi.org/10.1002/cbic.201600257
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author Johnston, Heather J.
Boys, Sarah K.
Makda, Ashraff
Carragher, Neil O.
Hulme, Alison N.
author_facet Johnston, Heather J.
Boys, Sarah K.
Makda, Ashraff
Carragher, Neil O.
Hulme, Alison N.
author_sort Johnston, Heather J.
collection PubMed
description Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid‐phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT116) cells was explored by reverse phase protein array (RPPA) analysis, which showed a dose‐dependent response in 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.
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spelling pubmed-50960272016-11-09 Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide Johnston, Heather J. Boys, Sarah K. Makda, Ashraff Carragher, Neil O. Hulme, Alison N. Chembiochem Full Papers Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid‐phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT116) cells was explored by reverse phase protein array (RPPA) analysis, which showed a dose‐dependent response in 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. John Wiley and Sons Inc. 2016-08-05 2016-09-02 /pmc/articles/PMC5096027/ /pubmed/27304907 http://dx.doi.org/10.1002/cbic.201600257 Text en © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Johnston, Heather J.
Boys, Sarah K.
Makda, Ashraff
Carragher, Neil O.
Hulme, Alison N.
Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide
title Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide
title_full Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide
title_fullStr Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide
title_full_unstemmed Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide
title_short Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide
title_sort naturally inspired peptide leads: alanine scanning reveals an actin‐targeting thiazole analogue of bisebromoamide
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096027/
https://www.ncbi.nlm.nih.gov/pubmed/27304907
http://dx.doi.org/10.1002/cbic.201600257
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