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Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides

The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. On the basis of genetic evidence, it has been postulated that the FHIT protein may function as tumor suppressor, implying a role for the FHIT protein in carcinogenesis. Recent...

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Autores principales: Scala, Maria Carmina, Di Micco, Simone, Lanzillotta, Delia, Musella, Simona, Di Sarno, Veronica, Parrino, Barbara, Cascioferro, Stella Maria, Bifulco, Giuseppe, Trapasso, Francesco, Campiglia, Pietro, Sala, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655160/
https://www.ncbi.nlm.nih.gov/pubmed/34901149
http://dx.doi.org/10.3389/fmolb.2021.715263
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author Scala, Maria Carmina
Di Micco, Simone
Lanzillotta, Delia
Musella, Simona
Di Sarno, Veronica
Parrino, Barbara
Cascioferro, Stella Maria
Bifulco, Giuseppe
Trapasso, Francesco
Campiglia, Pietro
Sala, Marina
author_facet Scala, Maria Carmina
Di Micco, Simone
Lanzillotta, Delia
Musella, Simona
Di Sarno, Veronica
Parrino, Barbara
Cascioferro, Stella Maria
Bifulco, Giuseppe
Trapasso, Francesco
Campiglia, Pietro
Sala, Marina
author_sort Scala, Maria Carmina
collection PubMed
description The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. On the basis of genetic evidence, it has been postulated that the FHIT protein may function as tumor suppressor, implying a role for the FHIT protein in carcinogenesis. Recently, Gaudio et al. reported that FHIT binds and delocalizes annexin A4 (ANXA4) from plasma membrane to cytosol in paclitaxel-resistant lung cancer cells, thus restoring their chemosensitivity to the drug. They also identified the smallest protein sequence of the FHIT still interacting with ANXA4, ranging from position 7 to 13: QHLIKPS. This short sequence of FHIT protein was not only able to bind ANXA4 but also to hold its target in the cytosol during paclitaxel treatment, thus avoiding ANXA4 translocation to the inner side of the cell membrane. Starting from these results, to obtain much information about structure requirements involved in the interaction of the peptide mentioned above, we synthetized a panel of seven peptides through an Ala-scan approach. In detail, to study the binding of FHIT derived peptides with ANXA4, we applied a combination of different biophysical techniques such as differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), and microscale thermophoresis (MST). Circular dichroism (CD) and nuclear magnetic resonance (NMR) were used to determine the conformational structure of the lead peptide (7–13) and peptides generated from ala-scan technique. The application of different biophysical and structural techniques, integrated by a preliminary biological evaluation, allowed us to build a solid structure activity relationship on the synthesized peptides.
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spelling pubmed-86551602021-12-10 Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides Scala, Maria Carmina Di Micco, Simone Lanzillotta, Delia Musella, Simona Di Sarno, Veronica Parrino, Barbara Cascioferro, Stella Maria Bifulco, Giuseppe Trapasso, Francesco Campiglia, Pietro Sala, Marina Front Mol Biosci Molecular Biosciences The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. On the basis of genetic evidence, it has been postulated that the FHIT protein may function as tumor suppressor, implying a role for the FHIT protein in carcinogenesis. Recently, Gaudio et al. reported that FHIT binds and delocalizes annexin A4 (ANXA4) from plasma membrane to cytosol in paclitaxel-resistant lung cancer cells, thus restoring their chemosensitivity to the drug. They also identified the smallest protein sequence of the FHIT still interacting with ANXA4, ranging from position 7 to 13: QHLIKPS. This short sequence of FHIT protein was not only able to bind ANXA4 but also to hold its target in the cytosol during paclitaxel treatment, thus avoiding ANXA4 translocation to the inner side of the cell membrane. Starting from these results, to obtain much information about structure requirements involved in the interaction of the peptide mentioned above, we synthetized a panel of seven peptides through an Ala-scan approach. In detail, to study the binding of FHIT derived peptides with ANXA4, we applied a combination of different biophysical techniques such as differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), and microscale thermophoresis (MST). Circular dichroism (CD) and nuclear magnetic resonance (NMR) were used to determine the conformational structure of the lead peptide (7–13) and peptides generated from ala-scan technique. The application of different biophysical and structural techniques, integrated by a preliminary biological evaluation, allowed us to build a solid structure activity relationship on the synthesized peptides. Frontiers Media S.A. 2021-11-25 /pmc/articles/PMC8655160/ /pubmed/34901149 http://dx.doi.org/10.3389/fmolb.2021.715263 Text en Copyright © 2021 Scala, Di Micco, Lanzillotta, Musella, Di Sarno, Parrino, Cascioferro, Bifulco, Trapasso, Campiglia and Sala. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Scala, Maria Carmina
Di Micco, Simone
Lanzillotta, Delia
Musella, Simona
Di Sarno, Veronica
Parrino, Barbara
Cascioferro, Stella Maria
Bifulco, Giuseppe
Trapasso, Francesco
Campiglia, Pietro
Sala, Marina
Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides
title Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides
title_full Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides
title_fullStr Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides
title_full_unstemmed Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides
title_short Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides
title_sort overcome chemoresistance: biophysical and structural analysis of synthetic fhit-derived peptides
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655160/
https://www.ncbi.nlm.nih.gov/pubmed/34901149
http://dx.doi.org/10.3389/fmolb.2021.715263
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