Ion-specificity in protein binding and recovery for the responsive hydrophobic poly(vinylcaprolactam) ligand

Liu, Zizhao; Wickramasinghe, S. Ranil; Qian, Xianghong

doi:10.1039/c7ra06022j

Cited by 11 publications

(19 citation statements)

References 41 publications

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“…The reduction of LCST is found to be strongly dependent on the salt-type and salt-concentration. The higher the ionic strength is, the larger the reduction will be. − It is also ion-specific with cations and anions each following a different order depending on the ionic charge and size. Our earlier studies ,, investigating the effects of salt ions on LCST transition of PNIPAM show that the cations tend to interact directly with the amide O. Anionic interaction with the polymer is mediated by the cations even though larger size anions form hydrophobic interaction with the isopropyl group on PNIPAM.…”

Section: Introductionmentioning

confidence: 99%

Atomistic Molecular Dynamics Simulations of the Lower Critical Solution Temperature Transition of Poly(N-vinylcaprolactam) in Aqueous Solutions

Sun

Qian

2019

J. Phys. Chem. B

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Poly(N-vinylcaprolactam) (PVCL) is a thermo-responsive polymer, which exhibits a lower critical solution temperature (LCST) in an aqueous solution. The LCST of this hydrophilic-to-hydrophobic transition is found to be strongly dependent on the salt-type and salt-concentration as well as on the molecular weight and concentration of the polymer. Here, atomistic molecular dynamics simulations have been successfully conducted for the first time to investigate the LCST transition of a 100 degree of polymerization PVCL chain in water, 1 M NaCl, 3.5 M NaCl, and 0.5 M CaCl2 solutions. Our results show that steric hindrance resulting from the bulky 7-member ring on the PVCL chain plays a critical role in the conformational transition. Moreover, the degrees of hydration and dehydration below or above the transition temperature are highly dependent on the specific solution condition and temperature. Water molecules are found to be trapped inside the collapsed polymer chains leading to the varying degrees of hydration and dehydration of the polymer chain in different solutions. Calculated water diffusion coefficients for both trapped and free water molecules agree very well with experimental measurements.

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Section: Introductionmentioning

confidence: 99%

Atomistic Molecular Dynamics Simulations of the Lower Critical Solution Temperature Transition of Poly(N-vinylcaprolactam) in Aqueous Solutions

Sun

Qian

2019

J. Phys. Chem. B

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“…The changes in conformation at the end of Helix-11 caused by the enlarged CoPP–Agonist-REV-ERBβ-LBD ( Figure 13 ) might weaken and negatively affect corepressor recruitment. Thus, the ligands might control the switch between open and closed conformations of the hydrophobic surface on the LBD for corepressor recruitment [ 27 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular Dynamics of Cobalt Protoporphyrin Antagonism of the Cancer Suppressor REV-ERBβ

et al. 2021

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Nuclear receptor REV-ERBβ is an overexpressed oncoprotein that has been used as a target for cancer treatment. The metal-complex nature of its ligand, iron protoporphyrin IX (Heme), enables the REV-ERBβ to be used for multiple therapeutic modalities as a photonuclease, a photosensitizer, or a fluorescence imaging agent. The replacement of iron with cobalt as the metal center of protoporphyrin IX changes the ligand from an agonist to an antagonist of REV-ERBβ. The mechanism behind that phenomenon is still unclear, despite the availability of crystal structures of REV-ERBβ in complex with Heme and cobalt protoporphyrin IX (CoPP). This study used molecular dynamic simulations to compare the effects of REV-ERBβ binding to Heme and CoPP, respectively. The initial poses of Heme and CoPP in complex with agonist and antagonist forms of REV-ERBβ were predicted using molecular docking. The binding energies of each ligand were calculated using the MM/PBSA method. The computed binding affinity of Heme to REV-ERBβ was stronger than that of CoPP, in agreement with experimental results. CoPP altered the conformation of the ligand-binding site of REV-ERBβ, disrupting the binding site for nuclear receptor corepressor, which is required for REV-ERBβ to regulate the transcription of downstream target genes. Those results suggest that a subtle change in the metal center of porphyrin can change the behavior of porphyrin in cancer cell signaling. Therefore, modification of porphyrin-based agents for cancer therapy should be conducted carefully to avoid triggering unfavorable effects.

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“…However, resin-based packed-bed chromatography suffers from high pressure drop and slow pore diffusion which leads to longer processing time and potentially denaturation of the product. Membrane adsorbers are promising technologies to replace resin-based chromatography [8][9][10][11][12][13][14]. Membrane-based IEX and HIC adsorbers can overcome afore-mentioned limitations [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…However, membrane capacity is typically lower compared to that of resin. Significant efforts have been dedicated to develop high binding capacity and/or high recovery membrane adsorbers by grafting ligands on membrane substrates using UV-initiated polymerization or atom-transfer radical polymerization (ATRP) [8][9][10][11][12][13][14][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies [24][25][26][27] conjugated a monomeric acid, base or affinity ligand directly to the functional group on the substrate. However, there has been significant work [8][9][10][11][12][13][14][17][18][19] on surface modification by grafting polymers on the flat sheet membrane substrates using ATRP and UV-initiated polymerizations. These results show that there exists an optimal ligand chain density and chain length for maximizing protein binding capacities for IEX, affinity and HIC membrane chromatography [19].…”

Section: Introductionmentioning

confidence: 99%

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Electrospun Weak Anion-Exchange Fibrous Membranes for Protein Purification

2020

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Membrane based ion-exchange (IEX) and hydrophobic interaction chromatography (HIC) for protein purification is often used to remove impurities and aggregates operated under the flow-through mode. IEX and HIC are also limited by capacity and recovery when operated under bind-and-elute mode for the fractionation of proteins. Electrospun nanofibrous membrane is characterized by its high surface area to volume ratio and high permeability. Here tertiary amine ligands are grafted onto the electrospun polysulfone (PSf) and polyacrylonitrile (PAN) membrane substrates using UV-initiated polymerization. Static and dynamic binding capacities for model protein bovine serum albumin (BSA) were determined under appropriate bind and elute buffer conditions. Static and dynamic binding capacities in the order of~100 mg/mL were obtained for the functionalized electrospun PAN membranes whereas these values reached~200 mg/mL for the functionalized electrospun PSf membranes. Protein recovery of over 96% was obtained for PAN-based membranes. However, it is only 56% for PSf-based membranes. Our work indicates that surface modification of electrospun membranes by grafting polymeric ligands can enhance protein adsorption due to increased surface area-to-volume ratio.

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Ion-specificity in protein binding and recovery for the responsive hydrophobic poly(vinylcaprolactam) ligand

Abstract: The conformational switch between the hydrophobic state and hydrophilic state of thermo-responsive poly(vinylcaprolactam) (PVCL) has great potential for protein purification as a hydrophobic interaction chromatography ligand.

Cited by 11 publications

References 41 publications

Atomistic Molecular Dynamics Simulations of the Lower Critical Solution Temperature Transition of Poly(N-vinylcaprolactam) in Aqueous Solutions

Atomistic Molecular Dynamics Simulations of the Lower Critical Solution Temperature Transition of Poly(N-vinylcaprolactam) in Aqueous Solutions

Molecular Dynamics of Cobalt Protoporphyrin Antagonism of the Cancer Suppressor REV-ERBβ

Electrospun Weak Anion-Exchange Fibrous Membranes for Protein Purification

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