Design and synthesis of enediyne-based peptide with selective peptide-cleaving activity

Roy, Snigdha; Basak, Amit

doi:10.1039/b923814j

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…Based on the ability of enediynes to react with proteinaceous substrates, ,− we evaluated the nanoparticles with Matrigel, a commonly used basement membrane extract . Nanoparticle samples were mixed with Matrigel stock solution (5 mg/mL final concentration) and warmed to 37 °C to allow the protein network to form.…”

Section: Resultsmentioning

confidence: 99%

Magnetically Triggered Radical-Generating Fe₃O₄ Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix

Walker

Zaleski

2015

Chem. Mater.

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Halting cancer progression by altering the tumor microenvironment is an exciting new frontier in oncology. One target for new therapies is the structural support provided by the extracellular matrix, which for cancer cells is often abnormal and undergoes drastic modification during angiogenesis, tumor proliferation, and metastasis. We have developed a new magnetic nanoparticle-based agent, Fe 3 O 4 −PEG−EDDA (EDDA: (Z)-octa-4-en-2,6-diyne-1,8-diamine), that is capable of generating radicals via Bergman cyclization of the pendant enediyne during mild hyperthermia treatment using an alternating magnetic field. We observe formation of a cyclized aromatic product in the Raman spectra of the thermally excited material and can detect polymeric product after periods of induction. When mixed with the basement membrane extract Matrigel, the nanoparticles do not interfere with normal biopolymer network formation. Applying the same hyperthermia conditions as in solution samples, Fe 3 O 4 −PEG−EDDA causes structural collapse of the matrix, visible by electron microscopy, in contrast to the nonradical-forming thermal control Fe 3 O 4 −PEG−BD (BD: o-xylylenediamine). Localized damage to the extracellular matrix by nanoparticle-induced molecular transformations represent a conceptual new tool in tumor microenvironment modification.

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Section: Resultsmentioning

confidence: 99%

Magnetically Triggered Radical-Generating Fe₃O₄ Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix

Walker

Zaleski

2015

Chem. Mater.

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“…In light of the activity of enediyne natural products toward biological substrates such as cellular DNA , and small peptides, − we investigated the action of Au-PEG-EDDA against a common blood protein: fibrin(ogen). Fibrin and its nonpolymerized hexamer glycoprotein precursor fibrinogen were subjected to three photolysis protocols in the presence of the gold nanoparticles synthesized above (Scheme ), whereas duplicate samples were held at room temperature for an equivalent period as controls.…”

Section: Resultsmentioning

confidence: 99%

Non-Enzymatic Remodeling of Fibrin Biopolymers via Photothermally Triggered Radical-Generating Nanoparticles

Walker

Zaleski

2014

Chem. Mater.

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Thrombosis is a hallmark of several chronic diseases leading to potentially fatal heart attacks and strokes. Frontline interventions include intravenous delivery of potent, enzymatic fibrinolytics that possess a high risk for inducing systemic bleeding. As a conceptual countermeasure, we have developed a water-soluble PEGylated gold nanoparticle appended with the enediyne diamine (Z)-octa-4-en-2,6-diyne-1,8-diamine that is capable of photothermally generating 1,4-diradical species under visible excitation (λ = 514 nm, 100 mW, 2−6 h). In the absence of biopolymer substrate, photothermal excitation of these particles leads to self-quenching polymer coating formation in water. When these radical-generating nanoparticles are intrinsically applied toward the blood clot structural protein assembly fibrin, as well as its nonpolymerized precursor protein fibrinogen, scanning electron microscopy images reveal significantly modified fibrin clot morphology, as evidenced by larger void spaces and collapsed fiber regions. Quantitatively, laser confocal microscopy images of Alexa Fluor 488-labeled fibrin clots extrinsically treated with nanoparticles at the clot/solution interface show that photothermal radical formation by these particles leads to marked increase in the number of larger pore sizes (>2.0 μm) within the fibrin matrix, which derive from a corresponding decrease in the histogram of smaller pore sizes (1.5−2.0 μm). These larger pore sizes ultimately result in total perfusion of solution through the entire clot volume. The chemical manifestation of this is that radical-induced modifications occur mainly at the protein level but lead to morphological changes at the micron scale. Overall, this technology could have significant impact for disease states such as deep vein thrombosis via a localized, catheter-delivered approach.

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“…Apart from their DNA damaging activity, the enediyne-derived diradicals have been shown to rupture the protein structure via oxidative cleavage of the peptide bond . This proteolytic activity also explains the resistance mechanism employed in pathogenic bacteria against such toxic secondary metabolites, e.g., calicheamicin γ 1 .…”

Section: Enediyne Warheadsmentioning

confidence: 99%

Photochemical Activation of Enediyne Warheads: A Potential Tool for Targeted Antitumor Therapy

et al. 2018

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Design and synthesis of enediyne-based peptide with selective peptide-cleaving activity

Abstract: A hybrid peptide-enediyne molecule was synthesised and shown to undergo selective intramolecular peptide chain cleavage by the 1,4-diyl radical, the potential intermediate of the enediyne system.

Cited by 9 publications

References 30 publications

Magnetically Triggered Radical-Generating Fe₃O₄ Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix

Magnetically Triggered Radical-Generating Fe₃O₄ Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix

Non-Enzymatic Remodeling of Fibrin Biopolymers via Photothermally Triggered Radical-Generating Nanoparticles

Photochemical Activation of Enediyne Warheads: A Potential Tool for Targeted Antitumor Therapy

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Design and synthesis of enediyne-based peptide with selective peptide-cleaving activity

Abstract: A hybrid peptide-enediyne molecule was synthesised and shown to undergo selective intramolecular peptide chain cleavage by the 1,4-diyl radical, the potential intermediate of the enediyne system.

Cited by 9 publications

References 30 publications

Magnetically Triggered Radical-Generating Fe3O4 Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix

Magnetically Triggered Radical-Generating Fe3O4 Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix

Non-Enzymatic Remodeling of Fibrin Biopolymers via Photothermally Triggered Radical-Generating Nanoparticles

Photochemical Activation of Enediyne Warheads: A Potential Tool for Targeted Antitumor Therapy

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Magnetically Triggered Radical-Generating Fe₃O₄ Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix

Magnetically Triggered Radical-Generating Fe₃O₄ Nanoparticles for Biopolymer Restructuring: Application to the Extracellular Matrix