Amphiphilic nature of polyethylene glycols and their role in medical research

Parray, Zahoor Ahmad; Hassan, Md. Imtaiyaz; Ahmad, Faizan; Islam, Asimul

doi:10.1016/j.polymertesting.2019.106316

Cited by 58 publications

(36 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Introductionmentioning

confidence: 99%

“…The PEG–protein interactions are feasible because of change in crowders hydrophilicity into amphiphilicity with increasing molecular weight of PEG (MW PEG ) 1 . Earlier it was assumed that no or very weak interaction occurs between PEG and proteins, however, the previously reported studies 1 – 10 gave new evidences that protein and PEG in aqueous solution holds various types of interactions. Such interactions are important not only for understanding the structural effects and changes in activity of proteins in solutions but also reliable to design materials for specific purposes 4 , 5 , 11 – 18 .…”

Section: Introductionmentioning

confidence: 99%

“…Such interactions are important not only for understanding the structural effects and changes in activity of proteins in solutions but also reliable to design materials for specific purposes 4 , 5 , 11 – 18 . PEGs are broadly used in a range of pharmaceutical formulations, including topical, parenteral, oral, ophthalmic and rectal preparations 1 , 17 . PEGs induce intermediate states (molten and pre-molten globules) in heme-proteins 2 , 4 , 5 , 10 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interaction of polyethylene glycol with cytochrome c investigated via in vitro and in silico approaches

Parray

Ahmad

Alajmi

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

One of the significant proteins that have attracted research groups due to virtue of being a potent selective anticancer drug target and property of triggering apoptosis upon release in cytoplasm is cytochrome c (cyt c). The mechanical transformations due to the macromolecular crowding in membrane in the mammalian cell are proposed to be useful inductors of changes in volume. It is very interesting to know that mitochondrial function were observed to be improved by polyethylene glycol (PEG) interaction, which in turn inhibits the cyt c (a pro-apoptotic cell death factor). In this work, the effect of polyethylene glycol of molecular weight 4 kilo Dalton (PEG 4 kDa) was investigated to highlight the structural transformations (tertiary and secondary structure) in cyt c using a choice of spectroscopic techniques (including UV–Vis absorption, near-UV, far-UV and Soret circular dichroism and fluorescence spectroscopy), which shows noteworthy shifts in the secondary and tertiary structures at higher concentrations of PEG 4 kDa with small changes in the heme-globular interactions. The size distribution changes of native protein treated with various concentrations of the crowder were observed and analyzed by dynamic light scattering (DLS). The interaction studies of the crowder with the protein was observed and analyzed by FTIR, isothermal titration calorimetry, time resolved fluorescence and molecular docking. The investigations suggested that the structural changes in the protein occurred due to soft interactions of PEG 4 kDa, which usually destabilizes proteins. The experimental evidence in this study proposed that crowding could be another approach to mechanical super-competition and free of certain markers that could aid in the identification and control of various diseases. This study suggests that crowders at specific concentrations, which softly interact with proteins, can be exploited as remedy for various diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interaction of polyethylene glycol with cytochrome c investigated via in vitro and in silico approaches

Parray

Ahmad

Alajmi

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The efficiency with which a nanoparticle is removed through complement activation is determined by its surface properties. The nanoparticle can be designed to have a surface that inhibits uptake, thus prolonging circulation in the bloodstream and, as a result, the amount of the drug that reaches the target tissue per administered dose; such a nanoparticle surface is referred to as a "stealth sheath" and the aforementioned PEGylation is the gold standard to achieve a this (Pasut and Veronese, 2012;Bunker, 2015;Parray et al, 2020). While PEGylation is an extremely successful strategy, it is not perfect and the investigation of alternate polymers to PEG is an active field of research (Knop et al, 2010).…”

Section: Nanoparticle Design and Functionmentioning

confidence: 99%

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

Bunker

Róg

2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

In this review, we outline the growing role that molecular dynamics simulation is able to play as a design tool in drug delivery. We cover both the pharmaceutical and computational backgrounds, in a pedagogical fashion, as this review is designed to be equally accessible to pharmaceutical researchers interested in what this new computational tool is capable of and experts in molecular modeling who wish to pursue pharmaceutical applications as a context for their research. The field has become too broad for us to concisely describe all work that has been carried out; many comprehensive reviews on subtopics of this area are cited. We discuss the insight molecular dynamics modeling has provided in dissolution and solubility, however, the majority of the discussion is focused on nanomedicine: the development of nanoscale drug delivery vehicles. Here we focus on three areas where molecular dynamics modeling has had a particularly strong impact: (1) behavior in the bloodstream and protective polymer corona, (2) Drug loading and controlled release, and (3) Nanoparticle interaction with both model and biological membranes. We conclude with some thoughts on the role that molecular dynamics simulation can grow to play in the development of new drug delivery systems.

show abstract

“…These intermediate structures in the cell influence these mechanisms to address emerging challenges in developing therapeutics and precision medicine [ 29 , 30 ]. To maintain the stability and function of different existing intermediate states (such as molten globule, pre-molten globule) various types of interactions (attractive and/or repulsive forces) play a significant role [ 15 , 22 , 24 , 31 , 32 , 33 ]. It has been reported that PEG-protein interaction induced contraction of NalD chains [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Structural Refolding and Thermal Stability of Myoglobin in the Presence of Mixture of Crowders: Importance of Various Interactions for Protein Stabilization in Crowded Conditions

et al. 2021

Self Cite

View full text Add to dashboard Cite

The intracellular environment is overcrowded with a range of molecules (small and large), all of which influence protein conformation. As a result, understanding how proteins fold and stay functional in such crowded conditions is essential. Several in vitro experiments have looked into the effects of macromolecular crowding on different proteins. However, there are hardly any reports regarding small molecular crowders used alone and in mixtures to observe their effects on the structure and stability of the proteins, which mimics of the cellular conditions. Here we investigate the effect of different mixtures of crowders, ethylene glycol (EG) and its polymer polyethylene glycol (PEG 400 Da) on the structural and thermal stability of myoglobin (Mb). Our results show that monomer (EG) has no significant effect on the structure of Mb, while the polymer disrupts its structure and decreases its stability. Conversely, the additive effect of crowders showed structural refolding of the protein to some extent. Moreover, the calorimetric binding studies of the protein showed very weak interactions with the mixture of crowders. Usually, we can assume that soft interactions induce structural perturbations while exclusion volume effects stabilize the protein structure; therefore, we hypothesize that under in vivo crowded conditions, both phenomena occur and maintain the stability and function of proteins.

show abstract

Amphiphilic nature of polyethylene glycols and their role in medical research

Cited by 58 publications

References 84 publications

Interaction of polyethylene glycol with cytochrome c investigated via in vitro and in silico approaches

Interaction of polyethylene glycol with cytochrome c investigated via in vitro and in silico approaches

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

Structural Refolding and Thermal Stability of Myoglobin in the Presence of Mixture of Crowders: Importance of Various Interactions for Protein Stabilization in Crowded Conditions

Contact Info

Product

Resources

About