Transport Behavior of the Enantiomers of Lactic Acid through the Cyclic Peptide Nanotube: Enantiomer Discrimination

Farrokhpour, Hossein; Mansouri, Alireza; Chermahini, Alireza Najafi

doi:10.1021/acs.jpcc.7b00010

Cited by 8 publications

(4 citation statements)

References 54 publications

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“…Sánchez-Quesada et al reported that unlike cyclic octapeptide nanotubes that lack glutamate transport activity, cyclic decapeptide nanotubes can allow the transport of glutamate ions from the inside of vesicles to the extravesicular region by measuring the glutamate transport rates across vesicular membranes . It has recently been demonstrated both experimentally and computationally that CPNs can be used as a potential drug delivery system through observations of the release of 5-fluorouracil, an anticancer drug, from liposomes through a cyclic decapeptide nanotube. ,, In addition, the transport behavior of simple organic molecules including ethanol and lactic acid through CPNs was studied using molecular dynamics (MD) simulations. ,,, d -Glucose (also known as d -glucopyranose), which is one of vital hydrophilic biomolecules, plays an important role in cell metabolism…”

Section: Introductionmentioning

confidence: 99%

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube: A Molecular Dynamics Simulation Study

et al. 2018

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The transport behavior of glucose through a cyclic peptide nanotube (CPN), composed of 8 × cyclo[-(Trp-d-Leu)-Gln-d-Leu-] rings embedded in DMPC lipid bilayers was examined using all-atom molecular dynamics (AAMD) simulations. Two conformational isomers of β-d-glucose, equatorial (C) and axial (C) chair conformers, were used to examine conformational effects on the hydrogen bond network, energetics, and diffusivity of glucose transport through the CPN. Calculations of the number of hydrogen bonds of the two glucose conformers with water molecules and with the CPN illustrate that the total number of hydrogen bonds of the conformers decreases inside the channel compared to bulk water due to the confinement characteristics of the interior of the CPNs although new hydrogen bonds between the hydroxyl and hydroxymethyl hydrogens of glucose and the carbonyl oxygens in the CPN backbone are formed. Despite the decrease of the number of hydrogen bonds inside the CPN, intramolecular hydrogen bonds of C are maintained during permeation of C through the CPN. The retention of intramolecular hydrogen bonds and the spherical shape of C give rise to considerably weaker orientational preferences and higher diffusion coefficients for C than those of C inside and outside the CPN. Due to larger dipole moments induced by the alignment of hydroxyl and hydroxymethyl groups, C has more favorable interactions with the CPN backbone at the channel entrances and inside the channel than C. In the middle of the CPN channel, entropic gains originating from higher orientational and translational degrees of freedom of C than those of C also contribute to lower free energy wells for C inside the CPN. This work reveals that the conformational variation and intramolecular hydrogen bond formation of β-d-glucose can have important effects on the energetics and dynamics of glucose transport through CPNs, providing insight into the translocation mechanism of d-glucose into the cell through glucose transporters (GLUTs) and the dynamics of glucose confined in silica nanochannels. It is also demonstrated that CPNs can indeed facilitate the permeation of small hydrophilic molecules such as glucose and can be utilized as a novel carrier system for hydrophilic drug compounds into the cell.

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Section: Introductionmentioning

confidence: 99%

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube: A Molecular Dynamics Simulation Study

et al. 2018

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“…The transportation of cations such as K + , − Na + , − Ca 2+ , and NH 4 + in CPNTs composed of varying peptides and configurations has been investigated using molecular dynamics simulations. Moreover, the movement of molecules including O 2 , CO 2 , NH 3 , , methane, methanol, , ethanol, , glucose, chloroform, ascorbic acid, lactic acid, and drugs like 5-fluorouracil , through CPNTs has been reported in the later years. Notably, many of these transport studies involved CPNTs embedded within lipid bilayers, predominantly within POPE bilayers.…”

Section: Introductionmentioning

confidence: 99%

Exploring Cyclic Peptide Nanotube Stability Across Diverse Lipid Bilayers and Unveiling Water Transport Dynamics

Moral,

Paul

2023

Langmuir

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Cyclic Peptide Nanotubes (CPNTs) have emerged as compelling candidates for various applications, particularly as nanochannels within lipid bilayers. In this study, the stability of two CPNTs, namely 8 × [(Cys-Gly-Met-Gly)2] and 8 × [(Gly-Leu)4], are comprehensively investigated across different lipid bilayers, including 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a mixed model membrane (POPE/POPG), and a realistic yeast model membrane. The results demonstrate that both CPNTs maintain their tubular structures in all lipid bilayers, with [(Cys-Gly-Met-Gly)2] showing increased stability over an extended period in these lipid membranes. The insertion of CPNTs shows negligible impact on lipid bilayer properties, including area per lipid, volume per lipid, and bilayer thickness. The study demonstrates that the CPNT preserves its two-line water movement pattern within all the lipid membranes, reaffirming their potential as water channels. The MSD curves further reveal that the dynamics of water molecules inside the nanotube are similar for all the bilayer systems with minor differences that arise due to different lipid environments.

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“…In the case of CPNs, MD simulations have been extensively utilized to examine the transport behavior of small biomolecules or organic molecules through the synthetic channel protein spanning across the lipid bilayers. For example, the permeation of biomolecules such as lactic acid and glucose through cyclic decapeptide nanotubes was scrutinized using MD simulations, which revealed that the energetic and dynamic properties of the molecules inside the CPNs depend on their isomeric composition. , …”

Section: Introductionmentioning

confidence: 99%

“…For example, the permeation of biomolecules such as lactic acid and glucose through cyclic decapeptide nanotubes was scrutinized using MD simulations, which revealed that the energetic and dynamic properties of the molecules inside the CPNs depend on their isomeric composition. 20,31 In this paper, we used all-atom MD (AAMD) simulations to examine the influence of the protonation state of glutamic acid on its transport through a cyclic decapeptide nanotube. In order to obtain the energetics and dynamic properties of the different charge states of the acid inside the CPN, the potential of mean force (PMF) and position-dependent diffusion coefficient profiles were calculated for the anionic, neutral zwitterionic, and cationic forms of glutamic acid.…”

Section: ■ Introductionmentioning

confidence: 99%

Molecular Dynamics Simulation Study of the Protonation State Dependence of Glutamic Acid Transport through a Cyclic Peptide Nanotube

et al. 2023

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The effect of the protonation state of glutamic acid on its translocation through cyclic peptide nanotubes (CPNs) was assessed by using molecular dynamics (MD) simulations. Anionic (GLU−), neutral zwitterionic (GLU0), and cationic (GLU+) forms of glutamic acid were selected as three different protonation states for an analysis of energetics and diffusivity for acid transport across a cyclic decapeptide nanotube. Based on the solubility-diffusion model, permeability coefficients for the three protonation states of the acid were calculated and compared with experimental results for CPN-mediated glutamate transport through CPNs. Potential of mean force (PMF) calculations reveal that, due to the cation-selective nature of the lumen of CPNs, GLU–, so-called glutamate, shows significantly high free energy barriers, while GLU+ displays deep energy wells and GLU0 has mild free energy barriers and wells inside the CPN. The considerable energy barriers for GLU– inside CPNs are mainly attributed to unfavorable interactions with DMPC bilayers and CPNs and are reduced by favorable interactions with channel water molecules through attractive electrostatic interactions and hydrogen bonding. Unlike the distinct PMF curves, position-dependent diffusion coefficient profiles exhibit comparable frictional behaviors regardless of the charge status of three protonation states due to similar confined environments imposed by the lumen of the CPN. The calculated permeability coefficients for the three protonation states clearly demonstrate that glutamic acid has a strong protonation state dependence for its transport through CPNs, as determined by the energetics rather than the diffusivity of the protonation state. In addition, the permeability coefficients also imply that GLU– is unlikely to pass through a CPN due to the high energy barriers inside the CPN, which is in disagreement with experimental measurements, where a considerable amount of glutamate permeating through the CPN was detected. To resolve the discrepancy between this work and the experimental observations, several possibilities are proposed, including a large concentration gradient of glutamate between the inside and outside of lipid vesicles and bilayers in the experiments, the glutamate activity difference between our MD simulations and experiments, an overestimation of energy barriers due to the artifacts imposed in MD simulations, and/or finally a transformation of the protonation state from GLU– to GLU0 to reduce the energy barriers. Overall, our study demonstrates that the protonation state of glutamic acid has a strong effect on the transport of the acid and suggests a possible protonation state change for glutamate permeating through CPNs.

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Transport Behavior of the Enantiomers of Lactic Acid through the Cyclic Peptide Nanotube: Enantiomer Discrimination

Cited by 8 publications

References 54 publications

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube: A Molecular Dynamics Simulation Study

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube: A Molecular Dynamics Simulation Study

Exploring Cyclic Peptide Nanotube Stability Across Diverse Lipid Bilayers and Unveiling Water Transport Dynamics

Molecular Dynamics Simulation Study of the Protonation State Dependence of Glutamic Acid Transport through a Cyclic Peptide Nanotube

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