Lysosome‐Targeted and Fluorescence‐Turned “On” Cytotoxicity Induced by Alkaline Phosphatase‐Triggered Self‐Assembly

2021 ◽  
pp. 2101346
Author(s):  
Chengfan Wu ◽  
Chenchen Wang ◽  
Tong Zhang ◽  
Ge Gao ◽  
Mengxing Wei ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Self Assembly

Interrelationship of the cellular distribution and secretion of regular structure (RS) protein in Bacillus licheniformis nm 105

1992 ◽  
Vol 50 (1) ◽  
pp. 712-713
Author(s):  
Xiaorong Zhu ◽  
Richard McVeigh ◽  
Bijan K. Ghosh
Keyword(s):  
Alkaline Phosphatase ◽  
Bacillus Licheniformis ◽  
Self Assembly ◽  
Gel Electrophoresis ◽  
Culture Supernatant ◽  
Regular Structure ◽  
The Self ◽  
Cellular Distribution ◽  
Structural Protein ◽  
Laboratory Cultures

A mutant of Bacillus licheniformis 749/C, NM 105 exhibits some notable properties, e.g., arrest of alkaline phosphatase secretion and overexpression and hypersecretion of RS protein. Although RS is known to be widely distributed in many microbes, it is rarely found, with a few exceptions, in laboratory cultures of microorganisms. RS protein is a structural protein and has the unusual properties to form aggregate. This characteristic may have been responsible for the self assembly of RS into regular tetragonal structures. Another uncommon characteristic of RS is that enhanced synthesis and secretion which occurs when the cells cease to grow. Assembled RS protein with a tetragonal structure is not seen inside cells at any stage of cell growth including cells in the stationary phase of growth. Gel electrophoresis of the culture supernatant shows a very large amount of RS protein in the stationary culture of the B. licheniformis. It seems, Therefore, that the RS protein is cotranslationally secreted and self assembled on the envelope surface.

Enzyme-instructed self-assembly enabled fluorescence light-up for alkaline phosphatase detection

Talanta ◽  
2021 ◽  
pp. 123078
Author(s):  
Yiming Zhang ◽  
Yinghao Ding ◽  
Xinxin Li ◽  
Zhenghao Zhang ◽  
Xiangyang Zhang ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Self Assembly ◽  
Fluorescence Light

Phosphobisaromatic motifs enable rapid enzymatic self-assembly and hydrogelation of short peptides

Soft Matter ◽  
2021 ◽  
Author(s):  
Meihui Yi ◽  
Jiaqi Guo ◽  
Hongjian He ◽  
Weiyi Tan ◽  
Nya Harmon ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Self Assembly ◽  
Soft Materials ◽  
Short Peptides

Enzyme-instructed self-assembly (EISA) and hydrogelation is a versatile approach for generating soft materials. Most of the substrates for alkaline phosphatase catalysed EISA utilizes phosphotyrosine (pTyr) as the enzymatic trigger for...

Polyphosphoric acid-induced perylene probe self-assembly and label-free fluorescence turn-on detection of alkaline phosphatase

2016 ◽  
Vol 409 (4) ◽  
pp. 1031-1036 ◽  
Author(s):  
Wenping Zhang ◽  
Ying Gao ◽  
Yongxin Li ◽  
Qingfeng Zhang ◽  
Zhenzhen Hu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Self Assembly ◽  
Polyphosphoric Acid ◽  
Label Free ◽  
Turn On ◽  
Fluorescence Turn On

scholarly journals Thiophosphopeptides Instantly Targeting Golgi Apparatus and Selectively Killing Cancer Cells

2021 ◽  
Author(s):  
Weiyi Tan ◽  
Qiuxin Zhang ◽  
Jiaqing Wang ◽  
Meihui Yi ◽  
Hongjian He ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Golgi Apparatus ◽  
Oxygen Atom ◽  
Cancer Cells ◽  
Self Assembly ◽  
Disulfide Bonds ◽  
Unexpected Result ◽  
Subcellular Compartment ◽  
Self Assembling ◽  
Order Of Magnitude

ABSTRACTGolgi apparatus is emerging as a key signaling hub of cells, but there are few approaches for targeting Golgi and selectively killing cancer cells. Here we show an unexpected result that changing an oxygen atom of the phosphoester bond in phospho-peptides by a sulfur atom enables instantly targeting Golgi apparatus (GA) and selectively killing cancer cells by enzymatic self-assembly. Specifically, conjugating cysteamine S-phosphate to the C-terminal of a self-assembling peptide generates a thiophospho-peptide. Being a substrate of alkaline phosphatase (ALP), the thiophosphopeptide undergoes rapid ALP-catalyzed dephosphorylation to form a thiopeptide that self-assembles. The thiophosphopeptide enters cells via caveolin-mediated endocytosis and macropinocytosis and instantly accumulates in GA because of dephosphorylation and formation of disulfide bonds in Golgi. Moreover, the thiophosphopeptide, targeting Golgi, potently and selectively inhibits cancer cells (e.g., HeLa) with the IC50 (about 3 μM), which is an order of magnitude more potent than that of the parent phosphopeptide. This work, as the first report of thiophospho-peptide for targeting Golgi, illustrates a new molecular platform for designing enzyme responsive molecules that target subcellular compartment for functions.

scholarly journals The Dynamic Continuum of Nanoscale Peptide Assemblies Facilitates Endocytosis and Endosomal Escape

2021 ◽  
Author(s):  
Hongjian He ◽  
Jiaqi Guo ◽  
Jiashu Xu ◽  
Jiaqing Wang ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Lipid Rafts ◽  
Self Assembly ◽  
Live Cell Imaging ◽  
Fluorescent Protein ◽  
Endosomal Escape ◽  
Hek293 Cells ◽  
Intracellular Targeting ◽  
Peptide Nanofibers ◽  
Effective Design

Considerable number of works have reported alkaline phosphatase (ALP) enabled intracellular targeting by peptide assemblies, but little is known how these substrates of ALP enters cells. Here we show that the nanoscale assemblies of phosphopeptides, as a dynamic continuum, cluster ALP to enable caveolae mediated endocytosis (CME) and eventual endosomal escape. Specifically, fluorescent phosphopeptides, as substrates of tissue nonspecific alkaline phosphatase (TNAP), undergo enzyme catalyzed self-assembly to form nanofibers. As shown by live cell imaging, the nanoparticles of phosphopeptides, being incubated with HEK293 cells overexpressing red fluorescent protein-tagged TNAP (TNAP-RFP), cluster TNAP-RFP in lipid rafts to enable CME, further dephosphorylation of the phosphopeptides form the peptide nanofibers for endosomal escape inside cells. Inhibiting TNAP, cleaving the membrane anchored TNAP, or disrupting lipid rafts abolishes the endocytosis. Moreover, decreasing the formation of peptide nanofibers prevents the endosomal escape. As the first study establishing a dynamic continuum of supramolecular assemblies for cellular uptake, this work not only illustrates an effective design for enzyme responsive supramolecular therapeutics, but also provides mechanism insights for understanding the dynamics of cellular uptakes of proteins or exogenous peptide aggregates at nanoscale.

scholarly journals Alkaline-phosphatase triggered self-assemblies enhances the anti-inflammatory property of methylprednisolone in spinal cord injury

2020 ◽  
Vol 18 ◽  
pp. 228080002097850 ◽  
Author(s):  
Haotao Yu ◽  
Ping Zhang ◽  
Wei Zhou ◽  
Zhihong Zhong ◽  
Dongbin Qu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Alkaline Phosphatase ◽  
Self Assembly ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Physical Strength ◽  
Cord Injury ◽  
Anti Inflammatory

Methylprednisolone sodium phosphate (MP) is an anti-inflammatory corticosteroid which is used in the treatment of spinal cord injury (SCI), however the overdose of MP has toxic effects Therefore it is prerequisite to develop novel approaches to overcome the side effects of MP and enhance its efficacy. In the present work, we have developed alkaline phosphatase (ALP) trigger self-assembly system of oligopeptides to physically entrap and locally deliver MP. The synthesis of Nap-Phe-Phe-Tyr(H2PO3)-OH (1P) was achieved using solid phase peptide synthesis and was characterized using mass spectroscopy. The 1P is a hydrogelator, which in presence of ALP self-assembles to form the hydrogel. During the self-assembly of 1P, MP was physically entrapped without losing the physical strength of hydrogel as revealed in the rheology study. The consistency of this hydrogel and the structure was characterized using circular dichroism. The MP was released from the hydrogel in a sustain manner and 80% of the drug release was observed at 120 h. The MP + 1P were non-toxic to the cells at lower concentration however toxicity increases with the increase in concentration of MP. Further, the in-vivo administration of MP + 1P significantly reduces the pro-inflammatory cytokines and the histological analysis revealed improvement in the SCI. In conclusion, it could be stated that the synthesis of 1P for the delivery of MP provides the novel opportunity in for the treatment of SCI.

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