Living cells reshape dynamic covalent chemical space via selective intracellular disulfide exchange
Abstract
Dynamic covalent chemistry (DCC) enables adaptive molecular systems, yet whether dynamic covalent networks can operate selectively inside living cells remains largely unknown. Here we show that living cells reshape dynamic covalent chemical space through selective intracellular disulfide exchange. A disulfide-based dynamic combinatorial library (DCL), previously characterized in vitro, undergoes cysteine-directed redistribution in cellular lysates and intact living cells. Fluorescence spectroscopy and live-cell ratiometric imaging reveal functional network reorganization, whereas UPLC–ESI-MS identifies specific species that provide orthogonal consistency with the optical response, including enrichment of a cysteine-containing heterotrimer and a fluorescent homodimer. Notably, this redistribution occurs despite millimolar glutathione and other competing intracellular thiols. These results establish living cells as chemically selective environments capable of biasing dynamic covalent networks, expanding DCC into functional intracellular contexts and providing a framework for target-guided molecular selection in situ.
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BibTeX
@misc{carbajo2026living,
title = {{Living cells reshape dynamic covalent chemical space via selective intracellular disulfide exchange}},
author = {Daniel Carbajo and Silvia Pujals and Jordi Solà and Ignacio Alfonso and IGNACIO ALFONSO},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15011131/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011131/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Living cells reshape dynamic covalent chemical space via selective intracellular disulfide exchange
AU - Daniel Carbajo
AU - Silvia Pujals
AU - Jordi Solà
AU - Ignacio Alfonso
AU - IGNACIO ALFONSO
PY - 2026
DA - 2026/10/27
PB - ChemRxiv
DO - 10.26434/chemrxiv.15011131/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011131/v1
AB - Dynamic covalent chemistry (DCC) enables adaptive molecular systems, yet whether dynamic covalent networks can operate selectively inside living cells remains largely unknown. Here we show that living cells reshape dynamic covalent chemical space through selective intracellular disulfide exchange. A disulfide-based dynamic combinatorial library (DCL), previously characterized in vitro, undergoes cysteine-directed redistribution in cellular lysates and intact living cells. Fluorescence spectroscopy and live-cell ratiometric imaging reveal functional network reorganization, whereas UPLC–ESI-MS identifies specific species that provide orthogonal consistency with the optical response, including enrichment of a cysteine-containing heterotrimer and a fluorescent homodimer. Notably, this redistribution occurs despite millimolar glutathione and other competing intracellular thiols. These results establish living cells as chemically selective environments capable of biasing dynamic covalent networks, expanding DCC into functional intracellular contexts and providing a framework for target-guided molecular selection in situ.
ER -