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bioRxiv · 10.64898/2026.07.24.740575

Total Synthesis of Self-Assembling Semi-Synthetic Proteins Utilizing a Dendritic Solubility Tag

Hati, K. C.·Sandanaraj, B.
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Abstract

The chemical synthesis of well-defined, self-assembling semi-synthetic proteins (SSPs) has attracted growing interest in recent years. Approaches such as micelle-assisted protein-labeling technology (MAPLabTech) and supramolecule-assisted protein-labeling technology (SAPLabTech) have been used to generate a wide range of SSPs. The central challenge in synthesizing SSPs is solubilizing a hydrophobic chemical probe in aqueous medium prior to bioconjugation. Both MAPLabTech and SAPLabTech rely on non-covalent interactions to solubilize hydrophobic probes and present certain limitations. The present study introduces a complementary chemical strategy in which a hydrophobic chemical probe is covalently tagged with a cleavable, water-soluble dendritic domain. This covalent tagging renders the probe fully water-soluble, enabling quantitative bioconjugation to yield monomeric semi-synthetic proteins. Subsequent, selective removal of the solubility tag converts the hydrophilic semi-synthetic proteins into facially amphiphilic, semi-synthetic proteins.

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Hati, K. C., Sandanaraj, B.. 2026-07-27. Total Synthesis of Self-Assembling Semi-Synthetic Proteins Utilizing a Dendritic Solubility Tag. https://doi.org/10.64898/2026.07.24.740575

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