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Nanomaterials
Volume 15
Issue 24
10.3390/nano15241846
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Antimicrobial Proteinoid Nanostructures via Thermal Condensation of L-Glutamic Acid and L-Tyrosine

by
Marta Cadeddu
1,
James R. G. Adams
2,
Roberto La Ragione
2,3,
Daniel K. Whelligan
4,
Vlad Stolojan
5,
Nadia Bernardi
2,
Ioannis Smyrnias
2,
Barbara Poddesu
6,
Giulia Cugia
6,
Davide De Forni
6,
Luca Malfatti
1,
Davide Carboni
1,*,
Alessandra Pinna
2,7,* and
Plinio Innocenzi
1,*
1
Laboratory of Materials Science and Nanotechnology, CR-INSTM, Department of Engineering, University of Sassari, Via Vienna 2, 07100 Sassari, Italy
2
Discipline of Comparative Biomedical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7AL, UK
3
Discipline of Microbes, Infection and Immunity, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7YH, UK
4
School of Chemistry and Chemical Engineering, University of Surrey, Guildford GU2 7YH, UK
5
Advanced Technology Institute (ATI), School of Computer Science and Electronic Engineering, University of Surrey, Guildford GU2 7YH, UK
6
ViroStatics S.r.l., Viale Umberto I, 46, 07100 Sassari, Italy
7
Department of Materials, Imperial College London, London SW7 2BX, UK
*
Authors to whom correspondence should be addressed.
Nanomaterials 2025, 15(24), 1846; https://doi.org/10.3390/nano15241846
Submission received: 24 October 2025 / Revised: 3 December 2025 / Accepted: 4 December 2025 / Published: 8 December 2025
(This article belongs to the Section Biology and Medicines)
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Abstract

The synthesis of biocidal peptide materials using simple, low-cost, solvent-free methods is a crucial challenge for developing new antimicrobial approaches. In this study, we produced proteinoid nanostructures through simple, inexpensive, and environmentally friendly thermal reactions between glutamic acid (Glu) and tyrosine (Tyr) in various molar ratios. Mechanistically, the thermal cyclization of glutamic acid into pyroglutamic acid (pGlu) facilitated the formation of short peptide chains containing pGlu as the N-terminus moiety and subsequent L-tyrosine or glutamic acid residues, which self-assembled into nanometric spheroidal structures that exhibit blue emission. Spectroscopic (FTIR, UV-Vis, photoluminescence) and mass (LC-MS) analyses confirmed the formation of mixed pGlu-/Tyr/Glu peptides. All products exhibit dose-dependent antimicrobial activity against Methicillin-Resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 25 mg mL−1 for the GluTyr 1:1 and 2:1 proteinoids. The outcomes observed following 24 h exposure of the HEK293 cell line to the materials indicate their suitability for integration into hybrid systems for antimicrobial surfaces. This work is the first to demonstrate a direct antibacterial activity of proteinoids obtained by thermal condensation, opening up the possibility of designing a new class of synthetic antimicrobial peptides.
Keywords: proteinoids; antimicrobial peptides; L-glutamic acid; L-tyrosine; nanomaterials; Staphylococcus proteinoids; antimicrobial peptides; L-glutamic acid; L-tyrosine; nanomaterials; Staphylococcus
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MDPI and ACS Style

Cadeddu, M.; Adams, J.R.G.; La Ragione, R.; Whelligan, D.K.; Stolojan, V.; Bernardi, N.; Smyrnias, I.; Poddesu, B.; Cugia, G.; De Forni, D.; et al. Antimicrobial Proteinoid Nanostructures via Thermal Condensation of L-Glutamic Acid and L-Tyrosine. Nanomaterials 2025, 15, 1846. https://doi.org/10.3390/nano15241846

AMA Style

Cadeddu M, Adams JRG, La Ragione R, Whelligan DK, Stolojan V, Bernardi N, Smyrnias I, Poddesu B, Cugia G, De Forni D, et al. Antimicrobial Proteinoid Nanostructures via Thermal Condensation of L-Glutamic Acid and L-Tyrosine. Nanomaterials. 2025; 15(24):1846. https://doi.org/10.3390/nano15241846

Chicago/Turabian Style

Cadeddu, Marta, James R. G. Adams, Roberto La Ragione, Daniel K. Whelligan, Vlad Stolojan, Nadia Bernardi, Ioannis Smyrnias, Barbara Poddesu, Giulia Cugia, Davide De Forni, and et al. 2025. "Antimicrobial Proteinoid Nanostructures via Thermal Condensation of L-Glutamic Acid and L-Tyrosine" Nanomaterials 15, no. 24: 1846. https://doi.org/10.3390/nano15241846

APA Style

Cadeddu, M., Adams, J. R. G., La Ragione, R., Whelligan, D. K., Stolojan, V., Bernardi, N., Smyrnias, I., Poddesu, B., Cugia, G., De Forni, D., Malfatti, L., Carboni, D., Pinna, A., & Innocenzi, P. (2025). Antimicrobial Proteinoid Nanostructures via Thermal Condensation of L-Glutamic Acid and L-Tyrosine. Nanomaterials, 15(24), 1846. https://doi.org/10.3390/nano15241846

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