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Enzyme-instructed self-assembly (EISA) and hydrogelation is a versatile approach for generating soft materials. Most of the substrates for alkaline phosphatase catalysed EISA utilize phosphotyrosine ( p Tyr) as the enzymatic trigger for EISA and hydrogelation. Here we show the first example of phosphonaphthyl ( p NP) and phosphobiphenyl ( p BP) motifs acting as faster enzymatic triggers than phosphotyrosine for EISA and hydrogelation. This work illustrates novel enzyme triggers for rapid enzymatic self-assembly and hydrogelation.
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Enzyme‐Instructed Self‐Assembly for Cellular Supramolecular Chemistry
ABSTRACT Enzyme‐instructed self‐assembly (EISA) uses endogenous enzymatic activity to convert soluble precursors into self‐assembling species, enabling the spatiotemporal formation of supramolecular nanostructures directly within cellular environments. Unlike other supramolecular strategies triggered by pH, redox, or light, EISA leverages the inherent spatial localization and dynamic kinetics of enzymes to achieve precise, context‐dependent control over where and when assembly occurs. While previous reviews have summarized EISA's mechanisms and biomedical applications, this perspective positions EISA as a conceptual framework for supramolecular chemical biology—emphasizing its role in mimicking higher‐order protein assemblies and in bridging molecular design with cellular function. We discuss how EISA enables programmable conformational and morphological switching, the creation of growth factor–mimicking assemblies, and the in situ formation of artificial supramolecular architectures inside or around cells. By highlighting EISA as a catalytic strategy for constructing functional supramolecular systems in vivo, this perspective outlines a new direction for integrating enzymatic control with nanoscale self‐organization in cellular supramolecular chemistry, generalizing EISA beyond alkaline phosphatases to programmable multi‐enzyme networks, and thereby advancing adaptive biomaterials, programmable therapeutics, and synthetic cellular machines.
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- Award ID(s):
- 2011846
- PAR ID:
- 10674302
- Publisher / Repository:
- Wiley-VCH
- Date Published:
- Journal Name:
- Chemistry – An Asian Journal
- Volume:
- 20
- Issue:
- 23
- ISSN:
- 1861-4728
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/asia.202500920
