Probing Polyethylene Glycol–Phospholipid Membrane Interactions Using Enzymes

Vijayalakshmi, A.; Krishnakumari, Viswanatha; Rao, Nalam Madhusudhana

doi:10.1006/jcis.1999.6471

Cited by 5 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interface is located at the end of a long hydrophobic channel that leads to the catalytic serine and to the oxyanion hole. Polyethylene glycol is known to activate the phospholipase activity of the enzyme, probably by stabilizing the interface complex between the lipase and the hydrophobic inner regions of cell membranes . To verify that PLA2G7 can accept 2cPE as a substrate, we have built a model of the tetrahedral covalent intermediate for the hydrolysis of 2c conjugated to an ethylene glycol dodecamer through the same succinate linker present in 2cPE.…”

Section: Resultsmentioning

confidence: 99%

“…Polyethylene glycol is known to activate the phospholipase activity of the enzyme, probably by stabilizing the interface complex between the lipase and the hydrophobic inner regions of cell membranes. 47 To verify that PLA2G7 can accept 2cPE as a substrate, we have built a model of the tetrahedral covalent intermediate for the hydrolysis of 2c conjugated to an ethylene glycol dodecamer through the same succinate linker present in 2cPE. The crystal structure of the paraoxon covalently inhibited enzyme was used as a starting point and stepwise mutated and optimized to build the model (see Supporting Information).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…43 In this manner we generated a list of 173 putative esterases. 47 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 24 The model confirms that 2cPE could be a substrate for phospholipase A2 secreted by A375 cells and thus supports the hypothesis that lack of this enzyme, or of other esterases that can activate the pro-drug, might explain the different low response of A549 and HT29 cell lines (Table 3). The expression of th...…”

Section: Assessmentmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent

et al. 2015

View full text Add to dashboard Cite

Bis-arylidenecycloalkanones structurally related to the nonselective isopeptidase inhibitor G5 were synthesized and tested for cytotoxic activity against glioblastoma cells. Cytotoxicities correlate well with Hammett σ constants for substituted arylidene groups, confirming the proposed inhibition mechanism. A new inhibitor (2c) based on the 4-hydroxycyclohexanone scaffold, which favors apoptosis over necrosis, was selected for further development. 2c inhibited representative deubiquitinases with micromolar IC50, and its proapoptotic activity was studied on several cancer cell lines. Inhibitor 2c was conjugated to PEG via dicarbamate and diester linkers. While the dicarbamate was inactive, the diester (2cPE) behaves like a prodrug and is converted into the active species 2c by secreted esterase activities. Finally, 2cPE was also tested in vivo on A549 lung carcinoma xenografts generated in mice. Intravenous treatment with 2cPE led to a significant reduction in primary tumor growth, without appreciable toxicity to mice.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Nevertless, in all in vitro gamete fusion low osmolarity is preferred, especially in PEG-mediated fusion. Significantly a recent study on PEG-membrane interaction, the effect of PEG on membranes was found to be independent of vesicle size (Vijayalakshmi et al 1999).…”

Section: Discussionmentioning

confidence: 92%

In vitro double fertilization in Nicotiana tabacum (L.): the role of cell volume in cell fusion

Sun

Moscatelli

Hong-yuan

et al. 2001

Sexual Plant Reproduction

View full text Add to dashboard Cite

The role of cell volume in regulating cell fusion was investigated by in vitro fertilization to elucidate mechanisms involved in double fertilization. The results revealed that in our model gamete fusion was more efficient than the fusion of somatic cells under the same conditions. The fusion of selected mesophyll protoplasts of different sizes and their fusion with chloroplasts demonstrated that cell volume ratio played a role in this process: as the ratio increased, fusion was more efficient and faster. When one of the cells was as small as a sperm, the formation of a round fusion product was faster. This might explain why gamete fusion was highly efficient in all in vitro germ cell fusion systems. This finding may also explain why sperm evolved as small cells. The results reported here will be useful for interpreting and evaluating data of in vitro fertilization experiments and for distinguishing gamete-specific characters.

show abstract

“…This indicated that all PEGs, irrespective of molecular weight and chain length, caused destabilization of the lipid monolayer, thus in apparent contradiction with the stabilization observed at low surface pressures for PEG with high molecular weights. However, studies by others have suggested that the dehydrating ability of PEGs would reduce the lipid molecular motion which may cause denser packing of the lipids and a decrease in the membrane fluidity [13,21].…”

Section: Discussionmentioning

confidence: 99%

Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?

et al. 2009

View full text Add to dashboard Cite

Polyethylene glycol (PEG), a high-molecularweight colloid present in new organ preservation solutions, protects against cold ischemia injuries leading to better graft function of transplanted organs. This protective effect cannot be totally explained by immuno-camouflaging property or signaling-pathway modifications. Therefore, we sought for an alternative mechanism dependent on membrane fluidity. Using the Langmuir-Pockles technique, we show here that PEGs interacted with lipid monolayers of defined composition or constituted by a renal cell lipid extract. High-molecular-weight PEGs stabilized the lipid monolayer at low surface pressure. Paradoxically, at high surface pressure, PEGs destabilized the monolayers. Hypothermia reduced the destabilization of saturated monolayer whereas unsaturated monolayer remained unaffected. Modification of ionic strength and pH induced a stronger stabilizing effect of PEG 35,000 Da which could explain its reported higher effectiveness on cold-induced injuries during organ transplantation. This study sheds a new light on PEG protective effects during organ preservation different from all classical hypotheses.

show abstract

Probing Polyethylene Glycol–Phospholipid Membrane Interactions Using Enzymes

Cited by 5 publications

References 28 publications

Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent

Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent

In vitro double fertilization in Nicotiana tabacum (L.): the role of cell volume in cell fusion

Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?

Contact Info

Product

Resources

About