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Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase

Recent findings qualified aldehydes as potential biomarkers for disease diagnosis. One of the possibilities is to use electrochemical biosensors in point-of-care (PoC), but these need further development to overcome some limitations. Currently, the primary goal is to enhance their metrological param...

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Autores principales: Wasilewski, Tomasz, Neubauer, Damian, Wojciechowski, Marek, Szulczyński, Bartosz, Gębicki, Jacek, Kamysz, Wojciech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342081/
https://www.ncbi.nlm.nih.gov/pubmed/37445789
http://dx.doi.org/10.3390/ijms241310610
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author Wasilewski, Tomasz
Neubauer, Damian
Wojciechowski, Marek
Szulczyński, Bartosz
Gębicki, Jacek
Kamysz, Wojciech
author_facet Wasilewski, Tomasz
Neubauer, Damian
Wojciechowski, Marek
Szulczyński, Bartosz
Gębicki, Jacek
Kamysz, Wojciech
author_sort Wasilewski, Tomasz
collection PubMed
description Recent findings qualified aldehydes as potential biomarkers for disease diagnosis. One of the possibilities is to use electrochemical biosensors in point-of-care (PoC), but these need further development to overcome some limitations. Currently, the primary goal is to enhance their metrological parameters in terms of sensitivity and selectivity. Previous findings indicate that peptide OBPP4 (KLLFDSLTDLKKKMSEC-NH(2)) is a promising candidate for further development of aldehyde-sensitive biosensors. To increase the affinity of a receptor layer to long-chain aldehydes, a structure stabilization of the peptide active site via the incorporation of different linkers was studied. Indeed, the incorporation of linkers improved sensitivity to and binding of aldehydes in comparison to that of the original peptide-based biosensor. The tendency to adopt disordered structures was diminished owing to the implementation of suitable linkers. Therefore, to improve the metrological characteristics of peptide-based piezoelectric biosensors, linkers were added at the C-terminus of OBPP4 peptide (KLLFDSLTDLKKKMSE-linker-C-NH(2)). Those linkers consist of proteinogenic amino acids from group one: glycine, L-proline, L-serine, and non proteinogenic amino acids from group two: β-alanine, 4-aminobutyric acid, and 6-aminohexanoic acid. Linkers were evaluated with in silico studies, followed by experimental verification. All studied linkers enhanced the detection of aldehydes in the gas phase. The highest difference in frequency (60 Hz, nonanal) was observed between original peptide-based biosensors and ones based on peptides modified with the GSGSGS linker. It allowed evaluation of the limit of detection for nonanal at the level of 2 ppm, which is nine times lower than that of the original peptide. The highest sensitivity values were also obtained for the GSGSGS linker: 0.3312, 0.4281, and 0.4676 Hz/ppm for pentanal, octanal, and nonanal, respectively. An order of magnitude increase in sensitivity was observed for the six linkers used. Generally, the linker’s rigidity and the number of amino acid residues are much more essential for biosensors’ metrological characteristics than the amino acid sequence itself. It was found that the longer the linkers, the better the effect on docking efficiency.
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spelling pubmed-103420812023-07-14 Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase Wasilewski, Tomasz Neubauer, Damian Wojciechowski, Marek Szulczyński, Bartosz Gębicki, Jacek Kamysz, Wojciech Int J Mol Sci Article Recent findings qualified aldehydes as potential biomarkers for disease diagnosis. One of the possibilities is to use electrochemical biosensors in point-of-care (PoC), but these need further development to overcome some limitations. Currently, the primary goal is to enhance their metrological parameters in terms of sensitivity and selectivity. Previous findings indicate that peptide OBPP4 (KLLFDSLTDLKKKMSEC-NH(2)) is a promising candidate for further development of aldehyde-sensitive biosensors. To increase the affinity of a receptor layer to long-chain aldehydes, a structure stabilization of the peptide active site via the incorporation of different linkers was studied. Indeed, the incorporation of linkers improved sensitivity to and binding of aldehydes in comparison to that of the original peptide-based biosensor. The tendency to adopt disordered structures was diminished owing to the implementation of suitable linkers. Therefore, to improve the metrological characteristics of peptide-based piezoelectric biosensors, linkers were added at the C-terminus of OBPP4 peptide (KLLFDSLTDLKKKMSE-linker-C-NH(2)). Those linkers consist of proteinogenic amino acids from group one: glycine, L-proline, L-serine, and non proteinogenic amino acids from group two: β-alanine, 4-aminobutyric acid, and 6-aminohexanoic acid. Linkers were evaluated with in silico studies, followed by experimental verification. All studied linkers enhanced the detection of aldehydes in the gas phase. The highest difference in frequency (60 Hz, nonanal) was observed between original peptide-based biosensors and ones based on peptides modified with the GSGSGS linker. It allowed evaluation of the limit of detection for nonanal at the level of 2 ppm, which is nine times lower than that of the original peptide. The highest sensitivity values were also obtained for the GSGSGS linker: 0.3312, 0.4281, and 0.4676 Hz/ppm for pentanal, octanal, and nonanal, respectively. An order of magnitude increase in sensitivity was observed for the six linkers used. Generally, the linker’s rigidity and the number of amino acid residues are much more essential for biosensors’ metrological characteristics than the amino acid sequence itself. It was found that the longer the linkers, the better the effect on docking efficiency. MDPI 2023-06-25 /pmc/articles/PMC10342081/ /pubmed/37445789 http://dx.doi.org/10.3390/ijms241310610 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wasilewski, Tomasz
Neubauer, Damian
Wojciechowski, Marek
Szulczyński, Bartosz
Gębicki, Jacek
Kamysz, Wojciech
Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase
title Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase
title_full Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase
title_fullStr Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase
title_full_unstemmed Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase
title_short Evaluation of Linkers’ Influence on Peptide-Based Piezoelectric Biosensors’ Sensitivity to Aldehydes in the Gas Phase
title_sort evaluation of linkers’ influence on peptide-based piezoelectric biosensors’ sensitivity to aldehydes in the gas phase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342081/
https://www.ncbi.nlm.nih.gov/pubmed/37445789
http://dx.doi.org/10.3390/ijms241310610
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