Chiral Linked Systems as a Model for Understanding D-Amino Acids Influence on the Structure and Properties of Amyloid Peptides

Ageeva, Aleksandra A.; Doktorov, A.B.; Polyakov, Nikolay E.; Leshina, Tatyana V.

doi:10.3390/ijms23063060

Cited by 5 publications

(5 citation statements)

References 35 publications

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“…The most popular spectroscopic techniques include circular dichroism (CD) to assess protein conformation [ 103 ] and Thioflavin T fluorescence, which is the most popular amyloid dye [ 104 ]. Other methods include infrared spectroscopy, nuclear magnetic resonance spectroscopy, or other types of fluorescence based on dyes or the intrinsic fluorescence of amino acids, especially tryptophan [ 105 ]. Clearly, the vast majority of these methods are indirect, and in any case, they do not provide information on the morphology of the aggregates, which is best assessed by microscopy techniques.…”

Section: Peptide Inhibitors Of Insulin Fibrillationmentioning

confidence: 99%

Peptide Inhibitors of Insulin Fibrillation: Current and Future Challenges

Rosetti

Marchesan

2023

IJMS

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Amyloidoses include a large variety of local and systemic diseases that share the common feature of protein unfolding or refolding into amyloid fibrils. The most studied amyloids are those directly involved in neurodegenerative diseases, while others, such as those formed by insulin, are surprisingly far less studied. Insulin is a very important polypeptide that plays a variety of biological roles and, first and foremost, is at the basis of the therapy of diabetic patients. It is well-known that it can form fibrils at the site of injection, leading to inflammation and immune response, in addition to other side effects. In this concise review, we analyze the current knowledge on insulin fibrillation, with a focus on the development of peptide-based inhibitors, which are promising candidates for their biocompatibility but still pose challenges to their effective use in therapy.

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Section: Peptide Inhibitors Of Insulin Fibrillationmentioning

confidence: 99%

Peptide Inhibitors of Insulin Fibrillation: Current and Future Challenges

Rosetti

Marchesan

2023

IJMS

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“…Glycation could affect the solubility of Aβ and, as a result, the ability of Aβ to form self-associates [ 12 ]. Another hypothesis explaining the self-association of Aβ is connected with the accumulation of D-amino acids in the Aβ structure [ 13 ]. Although, D-amino acids are studied as potential therapeutic agents against Alzheimer’s disease [ 14 , 15 ].…”

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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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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“…Second, this is the exploration of differences in the reactivity of systems with L- and D-amino acids [ 12 ]. It is crucial since replacing L-amino acids with D-analogs during aging causes Alzheimer’s and Parkinson’s diseases, type 2 diabetes, and several other ailments [ 16 , 17 , 18 ]. The presence of D-isomers of amino acids has been shown to result in disturbances in folding processes, leading to the aggregation of highly disordered amyloid proteins and peptides, forming large oligomers or fibrils, which have a toxic effect and destroy the brain.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of D-isomers of amino acids has been shown to result in disturbances in folding processes, leading to the aggregation of highly disordered amyloid proteins and peptides, forming large oligomers or fibrils, which have a toxic effect and destroy the brain. The current trend in studying the difference between L- and D-amino acids in highly disordered proteins and peptides is using short peptides as an example [ 17 , 18 ]. This approach to solving this problem is proposed in the literature since highly disordered proteins cannot be studied using high-resolution magnetic resonance and X-ray spectroscopy [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Photoinduced Processes in Lysine-Tryptophan-Lysine Tripeptide with L and D Tryptophan

Ageeva

Lukyanov

Martyanova

et al. 2023

IJMS

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Optical isomers of short peptide Lysine-Tryptophan-Lysine (Lys-{L/D-Trp}-Lys) and Lys-Trp-Lys with an acetate counter-ion were used to study photoinduced intramolecular and intermolecular processes of interest in photobiology. A comparison of L- and D-amino acid reactivity is also the focus of scientists’ attention in various specialties because today, the presence of amyloid proteins with D-amino acids in the human brain is considered one of the leading causes of Alzheimer’s disease. Since aggregated amyloids, mainly Aβ42, are highly disordered peptides that cannot be studied with traditional NMR and X-ray techniques, it is trending to explore the reasons for differences between L- and D-amino acids using short peptides, as in our article. Using NMR, chemically induced dynamic nuclear polarization (CIDNP) and fluorescence techniques allowed us to detect the influence of tryptophan (Trp) optical configuration on the peptides fluorescence quantum yields, bimolecular quenching rates of Trp excited state, and the photocleavage products formation. Thus, compared with the D-analog, the L-isomer shows a greater Trp excited state quenching efficiency with the electron transfer (ET) mechanism. There are experimental confirmations of the hypothesis about photoinduced ET between Trp and the CONH peptide bond, as well as between Trp and another amide group.

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Chiral Linked Systems as a Model for Understanding D-Amino Acids Influence on the Structure and Properties of Amyloid Peptides

Cited by 5 publications

References 35 publications

Peptide Inhibitors of Insulin Fibrillation: Current and Future Challenges

Peptide Inhibitors of Insulin Fibrillation: Current and Future Challenges

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

Photoinduced Processes in Lysine-Tryptophan-Lysine Tripeptide with L and D Tryptophan

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