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Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides
Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N(3))LARLLT and its cyclic analog cyclo(K(N(3))...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865655/ https://www.ncbi.nlm.nih.gov/pubmed/33498632 http://dx.doi.org/10.3390/molecules26030593 |
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author | Williams, Tyrslai M. Kaufman, Nichole E. M. Zhou, Zehua Singh, Sitanshu S. Jois, Seetharama D. Vicente, Maria da Graça H. |
author_facet | Williams, Tyrslai M. Kaufman, Nichole E. M. Zhou, Zehua Singh, Sitanshu S. Jois, Seetharama D. Vicente, Maria da Graça H. |
author_sort | Williams, Tyrslai M. |
collection | PubMed |
description | Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N(3))LARLLT and its cyclic analog cyclo(K(N(3))larllt, previously shown to have high affinity for binding to the extracellular domain of EGFR, were conjugated to alkynyl-functionalized BODIPY dyes 1 and 2 via a copper-catalyzed click reaction. This reaction produced conjugates 3, 4, and 5 in high yields (70–82%). In vitro studies using human carcinoma HEp2 cells that overexpress EGFR demonstrated high cellular uptake, particularly for the cyclic peptide conjugate 5, and low cytotoxicity in light (~1 J·cm(−2)) and darkness. Surface plasmon resonance (SPR) results show binding affinity of the three BODIPY-peptide conjugates for EGFR, particularly for 5 bearing the cyclic peptide. Competitive binding studies using three cell lines with different expressions of EGFR show that 5 binds specifically to EGFR-overexpressing colon cancer cells. Among the three conjugates, 5 bearing the cyclic peptide exhibited the highest affinity for binding to the EGFR protein. |
format | Online Article Text |
id | pubmed-7865655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78656552021-02-07 Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides Williams, Tyrslai M. Kaufman, Nichole E. M. Zhou, Zehua Singh, Sitanshu S. Jois, Seetharama D. Vicente, Maria da Graça H. Molecules Article Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N(3))LARLLT and its cyclic analog cyclo(K(N(3))larllt, previously shown to have high affinity for binding to the extracellular domain of EGFR, were conjugated to alkynyl-functionalized BODIPY dyes 1 and 2 via a copper-catalyzed click reaction. This reaction produced conjugates 3, 4, and 5 in high yields (70–82%). In vitro studies using human carcinoma HEp2 cells that overexpress EGFR demonstrated high cellular uptake, particularly for the cyclic peptide conjugate 5, and low cytotoxicity in light (~1 J·cm(−2)) and darkness. Surface plasmon resonance (SPR) results show binding affinity of the three BODIPY-peptide conjugates for EGFR, particularly for 5 bearing the cyclic peptide. Competitive binding studies using three cell lines with different expressions of EGFR show that 5 binds specifically to EGFR-overexpressing colon cancer cells. Among the three conjugates, 5 bearing the cyclic peptide exhibited the highest affinity for binding to the EGFR protein. MDPI 2021-01-23 /pmc/articles/PMC7865655/ /pubmed/33498632 http://dx.doi.org/10.3390/molecules26030593 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Williams, Tyrslai M. Kaufman, Nichole E. M. Zhou, Zehua Singh, Sitanshu S. Jois, Seetharama D. Vicente, Maria da Graça H. Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides |
title | Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides |
title_full | Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides |
title_fullStr | Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides |
title_full_unstemmed | Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides |
title_short | Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides |
title_sort | click conjugation of boron dipyrromethene (bodipy) fluorophores to egfr-targeting linear and cyclic peptides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865655/ https://www.ncbi.nlm.nih.gov/pubmed/33498632 http://dx.doi.org/10.3390/molecules26030593 |
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