ArticleJournal of the American Chemical Society2016
Enzyme-Instructed Self-Assembly of Small D-Peptides as a Multiple-Step Process for Selectively Killing Cancer Cells.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 237 citations in OpenAlex.
- Structure-Function Regulation of Proteolytically Stable Amphiphilic Peptide-Based Soft Materials With Antimicrobial Efficacy Against Drug-Resistant Strains and Anticancer Activity in Triple-Negative Breast Cancer Cells.Chembiochem : a European journal of chemical biology · 2026Article
- Evaluating Alkaline Phosphatase-Instructed Self-Assembly of d‑Peptide Diesters for Selectively Inhibiting Immunosuppressive Cancer Cells.ACS omega · 2026Article
- CD28-Targeted Enzyme-Responsive Conformation-Switching Peptide Self-Assembly for Selective T-Cell Acute Lymphoblastic Leukemia (T-ALL) Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cryo-Structural Insights into Enzymatic Peptide Self-Assembly Driving Extrinsic Lytic Cell Death.Journal of the American Chemical Society · 2026Article
- Targeting Subcellular Organelles in Breast Cancer with Enzyme Induced Self-Assembly: Stimulated Response with Eyes-Absence Enzymes (EYA).Molecular pharmaceutics · 2025Article
- Advances in Enzyme-responsive SupramolecularCurrent drug delivery · 2025Review
- Organelle-Specific Smart Supramolecular Materials for Bioimaging and Theranostics Application.Topics in current chemistry (Cham) · 2024Review
- Article
- Accelerating Cellular Uptake with Unnatural Amino Acid for Inhibiting Immunosuppressive Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Injectable Thermo-Responsive Peptide Hydrogels and Its Enzyme Triggered Dynamic Self-Assembly.Polymers · 2024Article
- Evaluating Alkaline Phosphatase-Instructed Self-Assembly of d-Peptides for Selectively Inhibiting Ovarian Cancer Cells.Journal of medicinal chemistry · 2023Article
- Enzyme-Triggered l-α/d-Peptide Hydrogels as a Long-Acting Injectable Platform for Systemic Delivery of HIV/AIDS Drugs.Advanced healthcare materials · 2023Article
- Article
- Designing supramolecular self-assembly nanomaterials as stimuli-responsive drug delivery platforms for cancer therapy.iScience · 2023Review
- Controlled sequential in situ self-assembly and disassembly of a fluorogenic cisplatin prodrug for cancer theranostics.Nature communications · 2023Article
- Encapsulation of Gold-Based Anticancer Agents in Protease-Degradable Peptide Nanofilaments Enhances Their Potency.Journal of the American Chemical Society · 2023Article
- Intracellular Enzyme-Instructed Self-Assembly of Peptides (IEISAP) for Biomedical Applications.Molecules (Basel, Switzerland) · 2022Review
- Enzyme Responsive Rigid-Rod Aromatics Target "Undruggable" Phosphatases to Kill Cancer Cells in a Mimetic Bone Microenvironment.Journal of the American Chemical Society · 2022Article
- Robust drug bioavailability and safety for rheumatoid arthritis therapy using D-amino acids-based supramolecular hydrogels.Materials today. Bio · 2022Article
- Investigating the role of peptides in effective therapies against cancer.Cancer cell international · 2022Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Selective inhibition of cancer cells remains a challenge in chemotherapy. Here we report the molecular and cellular validation of enzyme-instructed self-assembly (EISA) as a multiple step process for selectively killing cancer cells that overexpress alkaline phosphatases (ALPs). We design and synthesize two kinds of D-tetrapeptide containing one or two phosphotyrosine residues and with the N-terminal capped by a naphthyl group. Upon enzymatic dephosphorylation, these D-tetrapeptides turn into self-assembling molecules to form nanofibers in water. Incubating these D-tetrapeptides with several cancer cell lines and one normal cell line, the unphosphorylated D-tetrapeptides are innocuous to all the cell lines, the mono- and diphosphorylated D-tetrapeptides selectively inhibit the cancer cells, but not the normal cell. The monophosphorylated D-tetrapeptides exhibit more potent inhibitory activity than the diphosphorylated D-tetrapeptides do; the cancer cell lines express higher level of ALPs are more susceptible to inhibition by the phosphorylated D-tetrapeptides; the precursors of D-tetrapeptides that possess higher self-assembling abilities exhibit higher inhibitory activities. These results confirm the important role of enzymatic reaction and self-assembly. Using uncompetitive inhibitors of ALPs and fluorescent D-tetrapeptides, we delineate that the enzyme catalyzed dephosphorylation and the self-assembly steps, together, result in the localization of the nanofibers of D-tetrapeptides for killing the cancer cells. We find that the cell death modality likely associates with the cell type and prove the interactions between nanofibers and the death receptors. This work illustrates a paradigm-shifting and biomimetic approach and contributes useful molecular insights for the development of spatiotemporal defined supramolecular processes/assemblies as potential anticancer therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.