Probing the Role of Chirality in Phospholipid Membranes

Martin, Hannah S.; Podolsky, Kira A.; Devaraj, Neal K.

doi:10.1002/cbic.202100232

Cited by 24 publications

(18 citation statements)

References 71 publications

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“…Chiral lipid membranes can discriminate between amino acid enantiomers. A natural cellular membrane interacts more favorably with the L-enantiomer than the D amino acid [ 31 ]. Using a computer simulation, Chen et al have shown that L-peptides are absorbed easily by natural POPC membranes, but the D-peptides have to overcome an extra free-energy barrier [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

“…Note that membrane lipids and amino acids are almost ubiquitously homochiral within individual cells on Earth. A number of studies try to elucidate the determinants of stereospecific interactions between lipids, amino acids, and chiral drug molecules (see for example review [ 31 ]). Taking into account the results of previous studies of photoinduced electron transfer in diastereomers ketoprofen-tryptophan, in the present study we also use S-ketoprofen as an electron acceptor in photoinduced interaction with enantiomers of tryptophan, and CIDNP technique (chemically induced dynamic nuclear polarization) and molecular dynamics (MD) to study the peculiarities of their interaction in lipid membranes.…”

Section: Introductionmentioning

confidence: 99%

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Stereoselectivity of Interaction of Nonsteroidal Anti-Inflammatory Drug S-Ketoprofen with L/D-Tryptophan in Phospholipid Membranes

2022

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The mechanisms of stereoselectivity of the interaction of chiral drugs with active sites of enzymes and cell receptors attract significant attention. The first reason is the difference in therapeutic activity of the enantiomers of the common drugs. Another reason is the interest in the role of chiral inversion of amino acids involved in various peptides in the development of many diseases including Alzheimer’s, Parkinson’s, type II diabetes, and a number of other pathological conditions. In our study we use elementary chemical process—electron transfer (ET) to simulate individual stages of ligand–receptor and enzyme–substrate interactions. In particular, previous studies of photoinduced ET in chiral donor-acceptor dyads consisting of the nonsteroidal anti-inflammatory drug (R/S)-ketoprofen and (L)-tryptophan show the stereo and spin selectivity of ET in diastereomers. The present study is devoted to the interaction of (S)-ketoprofen with L- and D-enantiomers of tryptophan in homogeneous aqueous solution and in phospholipid membranes. The study was done using the NMR technique and molecular modeling. These approaches confirm efficient penetration of ketoprofen into the lipid bilayer and binding with tryptophan molecule. The short-lived paramagnetic intermediates formed during the photoinduced ET from electron donor tryptophan to ketoprofen have been detected using the chemically induced dynamic nuclear polarization (CIDNP) technique. It was found that S-ketoprofen interacts stereoselectively with tryptophan enantiomers in the lipid membrane. The formation of the ketyl radical of ketoprofen under irradiation leads to the oxidation of membrane lipids and may be the cause of ketoprofen phototoxicity. However, in contrast to a homogeneous solution in phosphate buffer saline, where the amino acid tryptophan accelerates the photodecomposition of KP due to intramolecular hydrogen transfer, tryptophan in a lipid membrane significantly reduces the rate of photodegradation due to a reversible electron (or hydrogen) transfer reaction. The stereoselectivity in the rate of KP and lipids decomposition under UV irradiation of S-ketoprofen in the presence of tryptophan enantiomers in lipid bilayer has been detected.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stereoselectivity of Interaction of Nonsteroidal Anti-Inflammatory Drug S-Ketoprofen with L/D-Tryptophan in Phospholipid Membranes

2022

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“…autophagy, apoptosis, cell growth, proliferation, and functions [145]. As a key component of cellular metabolism, mTOR integrates environmental stressors demand), cell physiology, and organism behavior.…”

Section: Universal Biological Of Agingmentioning

confidence: 99%

Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive, and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology

Dyakin¹,

Dyakina‐Fagnano²,

McIntire³

et al. 2021

Preprint

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In humans, age-associated degrading changes are observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psy-chological abilities, and memory. Cross talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, ge-nome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirali-ty, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging re-lated to irreversible PTMs SP has been associated with the nontrivial interplay between poor so-matic and mental health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet un-der-appreciated hallmark of aging.

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“…chirally matched combinations would have conducted to potent living systems whilst the chirally mismatched combinations would have declined. Such theory has notably been proposed recently to explain the splitting of lipids into opposite configurations in archaea and bacteria (known as the 'lipide divide') 521 and their persistence. 522 However, these theories do not address the fundamental question of the initial chiral bias and its enhancement.…”

Section: 520mentioning

confidence: 99%