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:	Maria Carmina Scala, Simone Di Micco, Delia Lanzillotta, Simona Musella, Veronica Di Sarno, Barbara Parrino, Stella Maria Casciofierro, Giuseppe Bifulco, Francesco Trapasso, Pietro Campiglia, Marina Sala
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	chemoresistance peptide FHIT annexin A4 biophysical assay Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f425afe0f6924c8c9422288e2c29eac7
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spelling	oai:doaj.org-article:f425afe0f6924c8c9422288e2c29eac72021-11-30T22:46:16ZOvercome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides2296-889X10.3389/fmolb.2021.715263https://doaj.org/article/f425afe0f6924c8c9422288e2c29eac72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.715263/fullhttps://doaj.org/toc/2296-889XThe 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.Maria Carmina ScalaSimone Di MiccoDelia LanzillottaSimona MusellaVeronica Di SarnoBarbara ParrinoStella Maria CasciofierroGiuseppe BifulcoFrancesco TrapassoPietro CampigliaMarina SalaFrontiers Media S.A.articlechemoresistancepeptideFHITannexin A4biophysical assayBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chemoresistance peptide FHIT annexin A4 biophysical assay Biology (General) QH301-705.5
spellingShingle	chemoresistance peptide FHIT annexin A4 biophysical assay Biology (General) QH301-705.5 Maria Carmina Scala Simone Di Micco Delia Lanzillotta Simona Musella Veronica Di Sarno Barbara Parrino Stella Maria Casciofierro Giuseppe Bifulco Francesco Trapasso Pietro Campiglia Marina Sala Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides
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.
format	article
author	Maria Carmina Scala Simone Di Micco Delia Lanzillotta Simona Musella Veronica Di Sarno Barbara Parrino Stella Maria Casciofierro Giuseppe Bifulco Francesco Trapasso Pietro Campiglia Marina Sala
author_facet	Maria Carmina Scala Simone Di Micco Delia Lanzillotta Simona Musella Veronica Di Sarno Barbara Parrino Stella Maria Casciofierro Giuseppe Bifulco Francesco Trapasso Pietro Campiglia Marina Sala
author_sort	Maria Carmina Scala
title	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_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_sort	overcome chemoresistance: biophysical and structural analysis of synthetic fhit-derived peptides
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f425afe0f6924c8c9422288e2c29eac7
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_version_	1718406237115121664

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

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