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Cited by 151RNA Interference and Gene DeliveryAldose Reductase and TaurineNanoparticle-Based Drug Delivery

Taurine Boosts Cellular Uptake of Small d -Peptides for Enzyme-Instructed Intracellular Molecular Self-Assembly

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Zhou, Jie, Du, Xuewen, Li, Jie, Yamagata, Natsuko, Xu, Bing·2015·Journal of the American Chemical Society
DOI 10.1021/jacs.5b06181PMC PMC4544318
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Abstract

Due to their biostability, d-peptides are emerging as an important molecular platform for biomedical applications. Being proteolytically resistant, d-peptides lack interactions with endogenous transporters and hardly enter cells. Here we show that taurine, a natural amino acid, drastically boosts the cellular uptake of small d-peptides in mammalian cells by >10-fold, from 118 μM (without conjugating taurine) to >1.6 mM (after conjugating taurine). The uptake of a large amount of the ester conjugate of taurine and d-peptide allows intracellular esterase to trigger intracellular self-assembly of the d-peptide derivative, further enhancing their cellular accumulation. The study on the mechanism of the uptake reveals that the conjugates enter cells via both dynamin-dependent endocytosis and macropinocytosis, but likely not relying on taurine transporters. Differing fundamentally from the positively charged cell-penetrating peptides, the biocompatibility, stability, and simplicity of the enzyme-cleavable taurine motif promise new ways to promote the uptake of bioactive molecules for countering the action of efflux pump and contributing to intracellular molecular self-assembly.

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  • Taurine can boost the cellular uptake of small D-peptides by endocytosis or trogocytosis.

    “It has been shown that taurine can boost the cellular uptake of small D-peptides by endocytosis or trogocytosis.81”

    From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [81]

    The Abstract reports that taurine conjugation boosts uptake of small D-peptides and identifies dynamin-dependent endocytosis and macropinocytosis as uptake pathways. It does not identify trogocytosis; the citing sentence appears to substitute that term for macropinocytosis. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
Zhou, J., Du, X., Li, J., Yamagata, N., & Xu, B.
Affiliations
Brandeis University (US)
Corresponding author
Xu, Bing
ORCID
Venue
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Published
2015-08-01
Volume
137
Issue
32
Pages
10040-10043
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
DOI
10.1021/jacs.5b06181
PMC
PMC4544318
OpenAlex
W1048568792
Cited by
151
References
0
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 13 · 2021: 16 · 2020: 21 · 2019: 16 · 2018: 18 · 2017: 16 · 2016: 21 · 2015: 6
FWCI
8.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American Chemical Society (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute (NA)
  • National Cancer Institute (R01CA142746)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
taurine, D-peptides, cellular uptake, intracellular self-assembly, intracellular esterases, endocytosis, macropinocytosis, enzyme-responsive drug delivery, cell-penetrating peptides
MeSH terms
Amiloride, Amino Acids, Buffers, Endocytosis, Esters, Fluorescence, HeLa Cells, Humans, 4-Chloro-7-nitrobenzofurazan, Taurine, Microscopy, Electron, Transmission, Cell-Penetrating Peptides

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