“Clicking” trimeric peptides onto hybrid T8POSS nanocages and identifying synthesis limitations

Lewis R. Anderson, Ann P. Hunter, Matthew J. Kershaw, Sergey Bylikin, James Bowen, Peter Taylor, Martin A. Birchall, Nazia Mehrban

Research output: Contribution to journalArticlepeer-review

Abstract

Macromolecule branching upon polyhedral oligomeric silsesquioxanes (POSS) via “click” chemistry has previously been reported for promoting natural biological responses in vitro, particularly when regarding their demonstrated biocompatibility and structural robustness as potential macromolecule anchoring points. However, “clicking” of large molecules around POSS structures uncovers two main challenges: (1) a synthetic challenge encompassing multi-covalent attachment of macromolecules to a single nanoscale-central position, and (2) purification and separation of fully adorned nanocages from those that are incomplete due to their similar physical characteristics. Here we present peptide decoration to a T8POSS nanocage through the attachment of azido-modified trimers. Triglycine- and trialanine-methyl esters “clicked” to 97% and 92% completion, respectively, resulting in 84% and 68% yields of the fully-adorned octamers. The “clicks” halt within 27-h of the reaction time, and efforts to further increase the octamer yield were of negligible benefit. Exploration of reaction conditions reveals multiple factors preventing full octa-arm modification to all available POSS nanocages, and offers insights into macromolecule attachment between both peptides and small inorganic-organic structures, all of which require consideration for future work of this nature.
Original languageEnglish
Pages (from-to)14802-14812
Number of pages11
JournalNanoscale
Volume16
Issue number31
Early online date11 Jul 2024
DOIs
Publication statusPublished - 21 Aug 2024

Data Availability Statement

The MALDI-TOF MS raw data obtained during this research is openly available from the University of Bath Research Data Archive at https://doi.org/10.15125/BATH-01390

Funding

This study was made possible through EPRSC funding (Grant No. EP/R02961X/1). The authors thank; NMSF, Swansea University Medical School, UK, for MALDI-TOF MS acquisition and processing; Mr Timothy Barton and Dr Samantha Hammond at the School of Environment, Earth and Ecosystem Sciences, The Open University, UK, for ICP-OES, ICP-MS and Chemical Analysis acquisition; Dr Zeeshan Mughal for technical assistance at the Electron Microscopy Suite, STEM, The Open University, UK, for EDX acquisition; Laboratory Management and Technicians at the School of Life, Health and Chemical Sciences, The Open University, UK, for laboratory and equipment access; Dr Simon Collinson at the School of Life, Health and Chemical Sciences, The Open University, UK, for visiting academic sponsorship; Ms Marie Caldiero at ESCOM Chimie, France, and Dr Erol Hasan of the National Physical Laboratory, UK, for their preliminary research contributions during the conceptualisation of this study.

FundersFunder number
EPRSCEP/R02961X/1

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