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Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process

[Image: see text] Synthetic peptides mimicking the binding site of fertilin β to its receptor, integrin α6β1, were shown to inhibit sperm–egg fusion when added to in vitro media. In contrast, the synthetic cyclic hexapeptide, cyclo(Cys(1)-Ser(2)-Phe(3)-Glu(4)-Glu(5)-Cys(6)), named as cFEE, proved to...

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Autores principales: Henández, Belén, Legrand, Pauline, Dufay, Sophie, Gahoual, Rabah, Sanchez-Cortes, Santiago, Kruglik, Sergei G., Fabreguettes, Jean-Roch, Wolf, Jean-Philippe, Houzé, Pascal, Ghomi, Mahmoud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843708/
https://www.ncbi.nlm.nih.gov/pubmed/31720508
http://dx.doi.org/10.1021/acsomega.9b01885
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author Henández, Belén
Legrand, Pauline
Dufay, Sophie
Gahoual, Rabah
Sanchez-Cortes, Santiago
Kruglik, Sergei G.
Fabreguettes, Jean-Roch
Wolf, Jean-Philippe
Houzé, Pascal
Ghomi, Mahmoud
author_facet Henández, Belén
Legrand, Pauline
Dufay, Sophie
Gahoual, Rabah
Sanchez-Cortes, Santiago
Kruglik, Sergei G.
Fabreguettes, Jean-Roch
Wolf, Jean-Philippe
Houzé, Pascal
Ghomi, Mahmoud
author_sort Henández, Belén
collection PubMed
description [Image: see text] Synthetic peptides mimicking the binding site of fertilin β to its receptor, integrin α6β1, were shown to inhibit sperm–egg fusion when added to in vitro media. In contrast, the synthetic cyclic hexapeptide, cyclo(Cys(1)-Ser(2)-Phe(3)-Glu(4)-Glu(5)-Cys(6)), named as cFEE, proved to stimulate gamete fusion. Owing to its biological specificity, this hexapeptide could help improve the in vitro fertilization pregnancy rate in human. In an attempt to establish the structure–activity relationship of cFEE, its structural dynamics was herein analyzed by means of ultraviolet circular dichroism (UV-CD) and Raman scattering. The low concentration CD profile in water, containing mainly a deep minimum at ∼202 nm, is consistent with a rather unordered chain. However, an ordering trend of the peptide loop has been observed in a less polar solvent such as methanol, where the UV-CD signal shape is formed by a double negative marker at ∼202/215 nm, indicating the presence of a type-II′ β-turn. Raman spectra recorded in aqueous samples upon a 100-fold concentration increase, still showed an important population (∼30%) of the disordered structure. The structural flexibility of the disulfide bridge was confirmed by the Raman markers arising from the Cys(1)-Cys(6) disulfide bond-stretch motions. Density functional theory calculations highlighted the formation of the type-II′ β-turn on the four central residues of cFEE (i.e., -Ser(2)-Phe(3)-Glu(4)-Glu(5)-) either with a left- or with a right-handed disulfide. The structure with a left-handed S–S bond, however, appears to be more stable.
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spelling pubmed-68437082019-11-12 Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process Henández, Belén Legrand, Pauline Dufay, Sophie Gahoual, Rabah Sanchez-Cortes, Santiago Kruglik, Sergei G. Fabreguettes, Jean-Roch Wolf, Jean-Philippe Houzé, Pascal Ghomi, Mahmoud ACS Omega [Image: see text] Synthetic peptides mimicking the binding site of fertilin β to its receptor, integrin α6β1, were shown to inhibit sperm–egg fusion when added to in vitro media. In contrast, the synthetic cyclic hexapeptide, cyclo(Cys(1)-Ser(2)-Phe(3)-Glu(4)-Glu(5)-Cys(6)), named as cFEE, proved to stimulate gamete fusion. Owing to its biological specificity, this hexapeptide could help improve the in vitro fertilization pregnancy rate in human. In an attempt to establish the structure–activity relationship of cFEE, its structural dynamics was herein analyzed by means of ultraviolet circular dichroism (UV-CD) and Raman scattering. The low concentration CD profile in water, containing mainly a deep minimum at ∼202 nm, is consistent with a rather unordered chain. However, an ordering trend of the peptide loop has been observed in a less polar solvent such as methanol, where the UV-CD signal shape is formed by a double negative marker at ∼202/215 nm, indicating the presence of a type-II′ β-turn. Raman spectra recorded in aqueous samples upon a 100-fold concentration increase, still showed an important population (∼30%) of the disordered structure. The structural flexibility of the disulfide bridge was confirmed by the Raman markers arising from the Cys(1)-Cys(6) disulfide bond-stretch motions. Density functional theory calculations highlighted the formation of the type-II′ β-turn on the four central residues of cFEE (i.e., -Ser(2)-Phe(3)-Glu(4)-Glu(5)-) either with a left- or with a right-handed disulfide. The structure with a left-handed S–S bond, however, appears to be more stable. American Chemical Society 2019-10-22 /pmc/articles/PMC6843708/ /pubmed/31720508 http://dx.doi.org/10.1021/acsomega.9b01885 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Henández, Belén
Legrand, Pauline
Dufay, Sophie
Gahoual, Rabah
Sanchez-Cortes, Santiago
Kruglik, Sergei G.
Fabreguettes, Jean-Roch
Wolf, Jean-Philippe
Houzé, Pascal
Ghomi, Mahmoud
Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process
title Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process
title_full Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process
title_fullStr Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process
title_full_unstemmed Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process
title_short Disorder-to-Order Markers of a Cyclic Hexapeptide Inspired from the Binding Site of Fertilin β Involved in Fertilization Process
title_sort disorder-to-order markers of a cyclic hexapeptide inspired from the binding site of fertilin β involved in fertilization process
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843708/
https://www.ncbi.nlm.nih.gov/pubmed/31720508
http://dx.doi.org/10.1021/acsomega.9b01885
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