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Nutrients Apr 2023The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting... (Review)
Review
The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting precursor of carnosine and is among the most used sports supplements for improving athletic performance. However, carnosine, its metabolite -acetylcarnosine, and the synthetic derivative zinc-L-carnosine have recently been gaining popularity as supplements in human medicine. These molecules have a wide range of effects-principally with anti-inflammatory, antioxidant, antiglycation, anticarbonylation, calcium-regulatory, immunomodulatory and chelating properties. This review discusses results from recent studies focusing on the impact of this supplementation in several areas of human medicine. We queried PubMed, Web of Science, the National Library of Medicine and the Cochrane Library, employing a search strategy using database-specific keywords. Evidence showed that the supplementation had a beneficial impact in the prevention of sarcopenia, the preservation of cognitive abilities and the improvement of neurodegenerative disorders. Furthermore, the improvement of diabetes mellitus parameters and symptoms of oral mucositis was seen, as well as the regression of esophagitis and taste disorders after chemotherapy, the protection of the gastrointestinal mucosa and the support of eradication treatment. However, in the areas of senile cataracts, cardiovascular disease, schizophrenia and autistic disorders, the results are inconclusive.
Topics: Humans; Carnosine; Antioxidants; Dietary Supplements; Dipeptides; Muscle, Skeletal; beta-Alanine
PubMed: 37049610
DOI: 10.3390/nu15071770 -
Journal of Nutritional Science and... 2022In the history of modern nutritional science, understanding antioxidants is one of the major topics. In many cases, food-derived antioxidants have π conjugate or thiol... (Review)
Review
In the history of modern nutritional science, understanding antioxidants is one of the major topics. In many cases, food-derived antioxidants have π conjugate or thiol group in their molecular structures because π conjugate stabilizes radical by its delocalization and two thiol groups form a disulfide bond in its antioxidative process. In recent years, antioxidant peptides have received much attention because for their ability to scavenge free radicals, inhibition of lipid peroxidation, chelation of transition metal ions, as well as their additional nutritional value. Among them, dipeptides are attracting much interest as post-amino acids, which have residues in common with amino acids, but also have different physiological properties and functions from those of amino acids. Especially, dipeptides containing moieties of several amino acid (tryptophan, tyrosine, histidine, cysteine, and methionine) possess potent antioxidant activity. This review summarizes previous details of structural property, radical scavenging activity, and biological activity of antioxidant dipeptide. Hopefully, this review will help provide a new insight into the study of the biological functions of antioxidant dipeptides.
Topics: Amino Acids; Antioxidants; Dipeptides; Food Additives; Lipid Peroxidation; Sulfhydryl Compounds
PubMed: 35768247
DOI: 10.3177/jnsv.68.162 -
Journal of Materials Chemistry. B Jun 2023Dipeptides are attractive building blocks for biomaterials in light of their inherent biocompatibility, biodegradability, and simplicity of preparation. Since the... (Review)
Review
Dipeptides are attractive building blocks for biomaterials in light of their inherent biocompatibility, biodegradability, and simplicity of preparation. Since the discovery of diphenylalanine (Phe-Phe) self-assembling ability into nanotubes, research efforts have been devoted towards the identification of other dipeptide sequences capable of forming these interesting nanomorphologies, although design rules towards nanotube formation are still elusive. In this review, we analyze the dipeptide sequences reported thus far for their ability to form nanotubes, which often feature water-filled supramolecular channels as revealed by single-crystal X-ray diffraction, as well as their properties, and their potential biological applications, which span from drug delivery and regenerative medicine, to bioelectronics and bioimaging.
Topics: Nanotubes; Water; Dipeptides; Models, Molecular; Hydrogen Bonding; Humans; Amino Acids
PubMed: 36790014
DOI: 10.1039/d2tb02643k -
Current Pharmaceutical Design 2018The article is an overview of author's data obtained in the framework of the project "The Creation of dipeptide preparations" at the V.V. Zakusov Institute of... (Review)
Review
The article is an overview of author's data obtained in the framework of the project "The Creation of dipeptide preparations" at the V.V. Zakusov Institute of Pharmacology, Moscow, Russia. Advantages of dipeptides over longer peptides consist in that they are orally active owing to higher stability and ability to penetrate biological barriers due to the presence of specific ATP-dependent transporters in enterocytes and blood-brain barrier. Two original approaches for dipeptide drugs design have been developed. Both of them are based on the idea of a leading role of central dipeptide fragment of the peptide chain beta-turn in the peptide-receptor interaction. The first approach, named "peptide drug-based design" represents the transformation of known nonpeptide drug into its dipeptide topological analog. The latter usually corresponds to a beta-turn of some regulatory peptide. The second approach represents the design of tripeptoide mimetic of the beta-turn of regulatory peptide or protein. The results of the studies, which led to the discovery of endogenous prototypes of the known non-peptide drugs piracetam and sulpiride, are presented herein. The paper discusses the process, based on the abovementioned principles, that was used in designing of nontoxic, orally available, highly effective dipeptide drugs: nootropic noopept, dipeptide analog of piracetam; antipsychotic dilept, neurotensin tripeptoid analog; selective anxiolytic GB-115, tripeptoid analog of CCK-4, and potential neuroprotector GK-2, homodimeric dipeptide analog of NGF.
Topics: Administration, Oral; Dipeptides; Drug Design; Humans; Molecular Structure
PubMed: 30295186
DOI: 10.2174/1381612824666181008105641 -
Advances in Nutrition (Bethesda, Md.) Oct 2022Carnosine is a pleiotropic histidine-containing dipeptide synthesized from β-alanine and l-histidine, with the intact dipeptide and constituent amino acids being... (Review)
Review
Carnosine is a pleiotropic histidine-containing dipeptide synthesized from β-alanine and l-histidine, with the intact dipeptide and constituent amino acids being available from the diet. The therapeutic application of carnosine in myocardial tissue is promising, with carnosine playing a potentially beneficial role in both healthy and diseased myocardial models. This narrative review discusses the role of carnosine in myocardial function and health, including an overview of the metabolic pathway of carnosine in the myocardial tissue, the roles carnosine may play in the myocardium, and a critical analysis of the literature, focusing on the effect of exogenous carnosine and its precursors on myocardial function. By so doing, we aim to identify current gaps in the literature, thereby identifying considerations for future research.
Topics: Amino Acids; Carnosine; Dipeptides; Histidine; Humans; Myocardium; beta-Alanine
PubMed: 35689661
DOI: 10.1093/advances/nmac059 -
The Journal of Organic Chemistry Jan 2022The (+) and (-) enantiomers of a new turn-inducing cyclopropyl dipeptide mimic have been synthesized and evaluated. The mimic derives its turn-inducing capabilities...
The (+) and (-) enantiomers of a new turn-inducing cyclopropyl dipeptide mimic have been synthesized and evaluated. The mimic derives its turn-inducing capabilities solely from the cyclopropyl group and without the conformational biasing that would be provided by side-chain substituents. The mimic and peptide-mimic hybrids prepared from it have been studied using a combination of spectroscopic techniques (NMR, IR, and CD). The dipeptide mimic itself displays intramolecular hydrogen bonding in organic solvents, which differs from that observed in natural peptide turns. In contrast, more elaborate peptide-mimic hybrids exhibit hydrogen bonding characteristics that vary with solvent but are consistent with structures found in the tetrapeptide portion ( → + 3) of a native β-turn.
Topics: Dipeptides; Hydrogen Bonding; Molecular Conformation; Peptides; Stereoisomerism
PubMed: 34913698
DOI: 10.1021/acs.joc.1c02344 -
The Journal of Organic Chemistry Oct 2021Ball milling of aromatic, heteroaromatic, vinylic, and aliphatic esters with ethanol and calcium nitride afforded the corresponding primary amides in a transformation...
Ball milling of aromatic, heteroaromatic, vinylic, and aliphatic esters with ethanol and calcium nitride afforded the corresponding primary amides in a transformation that was compatible with a variety of functional groups and maintained the integrity of a stereocenter α to carbonyl. This methodology was applied to α-amino esters and -BOC dipeptide esters and also to the synthesis of rufinamide, an antiepileptic drug.
Topics: Amides; Dipeptides; Esters
PubMed: 34596412
DOI: 10.1021/acs.joc.1c02350 -
Organic & Biomolecular Chemistry Aug 2022Dipeptides are convenient building blocks for supramolecular gel biomaterials that can be produced on a large scale at low cost and do not persist in the environment. In...
Dipeptides are convenient building blocks for supramolecular gel biomaterials that can be produced on a large scale at low cost and do not persist in the environment. In the case of unprotected sequences, hydrophobicity is a key requirement to enable gelation, with Phe-Phe standing out for its self-assembling ability. Conversely, more hydrophilic sequences such as homochiral dipeptides Phe-Val and Val-Phe neither fibrillate nor gel aqueous buffers and their crystal structures reveal amphipathic layers. In this work, we test emerging rules for the design of self-assembling dipeptides using heterochiral Phe-Val and Val-Phe. Each dipeptide is characterized by H- and C-NMR, LC-MS, circular dichroism, infrared and Raman spectroscopies, rheology, electron microscopy, and single-crystal X-ray diffraction. In particular, D-Phe-L-Val is the first heterochiral dipeptide to self-assemble into supramolecular water-channels whose cavity is defined by four peptide molecules arranged head-to-tail. This minimalistic sequence is devoid of amyloid character as probed by thioflavin T fluorescence and it displays excellent biocompatibility . The dataset provided, through comparison with the literature, significantly advances the definition of molecular design rules for minimalistic unprotected dipeptides that self-assemble into water-channels and biocompatible gels, to assist with the future development of supramolecular biomaterials with fine control over nanomorphological features for a variety of applications.
Topics: Biocompatible Materials; Dipeptides; Gels; Peptides; Water
PubMed: 35575102
DOI: 10.1039/d2ob00622g -
American Journal of Physiology. Cell... Feb 2022Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have been thought as two distinct neurodegenerative diseases. However, recent genetic screening and... (Review)
Review
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have been thought as two distinct neurodegenerative diseases. However, recent genetic screening and careful investigations found the genetic and pathological overlap among these disorders. Hexanucleotide expansions in intron 1 of are a leading cause of familial ALS and familial FTD. These expansions facilitate the repeat-associated non-ATG-initiated translation (RAN translation), producing five dipeptide repeat proteins (DRPs), including Arg-rich poly(PR: Pro-Arg) and poly(GR: Gly-Arg) peptides. Arg is a positively charged, highly polar amino acid that facilitates interactions with anionic molecules such as nucleic acids and acidic amino acids via electrostatic forces and aromatic amino acids via cation-π interaction, suggesting that Arg-rich DRPs underlie the pathophysiology of ALS via Arg-mediated molecular interactions. Arg-rich DRPs have also been reported to induce neurodegeneration in cellular and animal models via multiple mechanisms; however, it remains unclear why the Arg-rich DRPs exhibit such diverse toxic properties, because not all Arg-rich peptides are toxic. In this mini-review, we discuss the current understanding of the pathophysiology of Arg-rich C9ORF72 DRPs and introduce recent findings on the role of Arg distribution as a determinant of the toxicity and its contribution to the pathogenesis of ALS.
Topics: Amyotrophic Lateral Sclerosis; Animals; C9orf72 Protein; Dipeptides; Frontotemporal Dementia; Humans; Neurodegenerative Diseases; Peptide Fragments; Structure-Activity Relationship
PubMed: 34910602
DOI: 10.1152/ajpcell.00372.2021 -
Macromolecular Rapid Communications Feb 2023Mixing low molecular weight gelators (LMWGs) can be used to combine favorable properties of the individual components within a multifunctional gel. Such multicomponent...
Mixing low molecular weight gelators (LMWGs) can be used to combine favorable properties of the individual components within a multifunctional gel. Such multicomponent systems are complex enough in themselves but the method of combining components is not commonly considered something to influence self-assembly. Herein, two multicomponent systems comprising of a naphthalene-based dipeptide hydrogelator and one of two modified naphthalene diimides (NDIs), one of which forms gels, and the other does not, are investigated. These systems are probed, examining the structures formed and their gel properties (when preparing a solution from either a mixed powder of both components or by mixing pre-formed solutions of each component) using rheology, small angle neutron scattering (SANS), and absorbance spectroscopy. It is found that by altering the method of preparation, it is can either induce self-sorting or co-assembly within the fibers formed that underpin the gel network.
Topics: Gels; Dipeptides; Spectrum Analysis
PubMed: 36177680
DOI: 10.1002/marc.202200709