Self-assembly and cytocompatibility of amino acid conjugates containing a novel water-soluble aromatic protecting group

Castelletto, V. ORCID: https://orcid.org/0000-0002-3705-0162, de Mello, L., da Silva, E. R. ORCID: https://orcid.org/0000-0001-5876-2276, Seitsonen, J. and Hamley, I. W. ORCID: https://orcid.org/0000-0002-4549-0926 (2023) Self-assembly and cytocompatibility of amino acid conjugates containing a novel water-soluble aromatic protecting group. Biomacromolecules, 24 (11). pp. 5403-5413. ISSN 1526-4602 doi: 10.1021/acs.biomac.3c00860

Abstract/Summary

There has been considerable interest in peptides in which the Fmoc (9-fluorenylmethoxycarbonyl) protecting group is retained at the N-terminus, since this bulky aromatic group can drive self-assembly, and Fmoc-peptides are biocompatible and have applications in cell culture biomaterials. Recently, analogues of new amino acids with 2,7-disulfo-9-fluorenylmethoxycarbonyl (Smoc) protecting groups have been developed for water-based peptide synthesis. Here, we report on the self-assembly and biocompatibility of Smoc-Ala, Smoc-Phe and Smoc-Arg as examples of Smoc conjugates to aliphatic, aromatic, and charged amino acids, respectively. Self-assembly occurs at concentrations above the critical aggregation concentration (CAC). Cryo-TEM imaging and SAXS reveal the presence of nanosheet, nanoribbon or nanotube structures, and spectroscopic methods (ThT fluorescence circular dichroism and FTIR) show the presence of β-sheet secondary structure, although Smoc-Ala solutions contain significant unaggregated monomer content. Smoc shows self-fluorescence, which was used to determine CAC values of the Smoc-amino acids from fluorescence assays. Smoc fluorescence was also exploited in confocal microscopy imaging with fibroblast cells, which revealed its uptake into the cytoplasm. The biocompatibility of these Smoc-amino acids was found to be excellent with zero cytotoxicity (in fact increased metabolism) to fibroblasts at low concentration.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/113843
Identification Number/DOI	10.1021/acs.biomac.3c00860
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	American Chemical Society
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