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Peptide-Based Fluorescent Biosensing System for the Detection of the Melanoma Biomarker S100B

Lookup NU author(s): Dr Othman AlmusaimiORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Cutaneous melanoma, responsible for 80% of skin cancer mortality, presents urgent diagnostic challenges due to insufficient early detection methods. Current clinical methods rely on invasive biopsies, while noninvasive approaches primarily serve as adjunctive decision-support tools rather than definitive diagnostics. Here, a peptide-based fluorescent biosensing system was developed for the sensitive and rapid detection of S100B, a key prognostic biomarker for melanoma. Our system employs a fluorescently labeled peptide beacon designed for Förster resonance energy transfer (FRET)-based detection, achieving a subnanomolar detection limit (∼0.045 nM) and great selectivity in human serum samples. Peptide synthesis was performed using optimized solid-phase protocols, enabling precise sequence assembly, while the peptide sensor offers efficient detection, lower costs, and high specificity through tailored peptide–protein interactions. The biosensing probe employs complementary peptide nucleic acid (PNA) interactions to achieve proximity-induced fluorescence quenching in the absence of S100B, which reverses via structural rearrangement upon specific S100B binding for accurate quantification. Computational and experimental optimization of the synthetic process has enhanced binding efficiency, sensitivity, and response time–crucial parameters for melanoma-specific detection. By integrating advanced molecular design with optical biosensing, this mechanism aims to enhance the accuracy and accessibility of melanoma diagnostics, ultimately addressing healthcare disparities and improving patient outcomes.


Publication metadata

Author(s): Chatzilakou E, Hu Y, Al Musaimi O, Valenzo O, Jiang N, Williams DR, Yetisen AK

Publication type: Article

Publication status: Published

Journal: Bioconjugate Chemistry

Year: 2025

Volume: 36

Issue: 11

Pages: 2357-2369

Print publication date: 19/11/2025

Online publication date: 06/11/2025

Acceptance date: 30/10/2025

Date deposited: 28/11/2025

ISSN (print): 1043-1802

ISSN (electronic): 1520-4812

Publisher: American Chemical Society

URL: https://doi.org/10.1021/acs.bioconjchem.5c00337

DOI: 10.1021/acs.bioconjchem.5c00337

Data Access Statement: The data supporting this article have been included as part of the Supporting Information. The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.bioconjchem.5c00337


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Funding

Funder referenceFunder name
Elena Iliopoulou Giama Cancer Research & Scholarship Foundation
MISTI Global Seed Funds for the MIT-Imperial College London Seed Fund 2023

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