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Marine Drugs Aug 2022The extensive use of conventional antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. Evidence suggests that cationic...
The extensive use of conventional antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. Evidence suggests that cationic antimicrobial peptides (AMPs) have the greatest potential to serve as traditional antibiotic substitutes. Recent studies have also reported that certain AMPs have selective toxicity toward various types of cancer cells. The electrostatic attraction between the negatively charged membrane components and AMPs is believed to play a crucial role in the disruption of bacterial and cancer cell membranes. In the current study, we used a potent AMP called Pleurocidin (Ple) derived from winter flounder and its C-terminal-amidated derivative Pleurocidin-amide (Ple-a), and evaluated their antibacterial and anticancer activities. Our results indicated that both Ple and Ple-a exhibited significant antibacterial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, especially marine pathogens, with MIC values ranging from 0.25 to 32 μg/mL. These peptides are also potent against several multidrug-resistant (MDR) bacterial strains, with MIC values ranging from 2 to 256 μg/mL. When used in combination with certain antibiotics, they exhibited a synergistic effect against MDR . Ple and Ple-a also showed notable cytotoxicity toward various cancer cell lines, with IC values ranging from 11 to 340 μM, while normal mouse fibroblast 3T3 cells were less susceptible to these peptides. Ple-a was then selected to study its anticancer mechanism toward A549 human lung adenocarcinoma cells. Western blot analysis and confocal microscopy showed that Ple-a could inhibit autophagy of A549 cells, and induce apoptosis 48 h after treatment. Our findings provided support for the future application of Ple-a as potential therapeutic agent for bacterial infections and cancer treatment.
Topics: Amides; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Antimicrobial Peptides; Bacteria; Escherichia coli; Fish Proteins; Flounder; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Mice; Microbial Sensitivity Tests
PubMed: 36005521
DOI: 10.3390/md20080519 -
ChemistryOpen Oct 2022Introduction of adamantane moieties on diamondoids such as adamantane, 2-azaadamantane or diamantane by amide formation and reduction to the corresponding amine was...
Introduction of adamantane moieties on diamondoids such as adamantane, 2-azaadamantane or diamantane by amide formation and reduction to the corresponding amine was performed in a straightforward and easy way by amidation under Schotten-Baumann conditions and reduction with BH ⋅ THF. The obtained amides and amines were studied in terms of structural properties towards the perspective of transformation into nanodiamonds. Crystal structure and dynamic NMR experiments of the most crowded amide obtained gave structural insights into the effect of bulkiness and steric strain on out-of-planarity of amide bonds (16.0°) and the kinetics and thermodynamics of amide bond rotation (ΔG =11.5-13.3 kcal ⋅ mol ).
Topics: Adamantane; Amides; Amines; Nanodiamonds; Thermodynamics
PubMed: 35243816
DOI: 10.1002/open.202200031 -
Acta Crystallographica. Section C,... Feb 2016Carbamazepine (CBZ) is well known as a model active pharmaceutical ingredient used in the study of polymorphism and the generation and comparison of cocrystal forms. The...
Carbamazepine (CBZ) is well known as a model active pharmaceutical ingredient used in the study of polymorphism and the generation and comparison of cocrystal forms. The pharmaceutical amide dihydrocarbamazepine (DCBZ) is a less well known material and is largely of interest here as a structural congener of CBZ. Reaction of DCBZ with strong acids results in protonation of the amide functionality at the O atom and gives the salt forms dihydrocarbamazepine hydrochloride {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride, C15H15N2O(+)·Cl(-)}, dihydrocarbamazepine hydrochloride monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride monohydrate, C15H15N2O(+)·Cl(-)·H2O} and dihydrocarbamazepine hydrobromide monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium bromide monohydrate, C15H15N2O(+)·Br(-)·H2O}. The anhydrous hydrochloride has a structure with two crystallographically independent ion pairs (Z' = 2), wherein both cations adopt syn conformations, whilst the two hydrated species are mutually isostructural and have cations with anti conformations. Compared to neutral dihydrocarbamazepine structures, protonation of the amide group is shown to cause changes to both the molecular (C=O bond lengthening and C-N bond shortening) and the supramolecular structures. The amide-to-amide and dimeric hydrogen-bonding motifs seen for neutral polymorphs and cocrystalline species are replaced here by one-dimensional polymeric constructs with no direct amide-to-amide bonds. The structures are also compared with, and shown to be closely related to, those of the salt forms of the structurally similar pharmaceutical carbamazepine.
Topics: Amides; Azepines; Carbamazepine; Crystallization; Crystallography, X-Ray; Hydrogen Bonding; Molecular Structure
PubMed: 26846502
DOI: 10.1107/S2053229616001133 -
Journal of Visualized Experiments : JoVE Jun 2014Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using...
Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using combinatorial chemistry. One of the most well studied classes of peptidomimetics is peptoids. Peptoids are easy to synthesize and have been shown to be proteolysis-resistant and cell-permeable. Over the past decade, many useful protein ligands have been identified through screening of peptoid libraries. However, most of the ligands identified from peptoid libraries do not display high affinity, with rare exceptions. This may be due, in part, to the lack of chiral centers and conformational constraints in peptoid molecules. Recently, we described a new synthetic route to access peptide tertiary amides (PTAs). PTAs are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. With side chains on both α-carbon and main chain nitrogen atoms, the conformation of these molecules are greatly constrained by sterical hindrance and allylic 1,3 strain. (Figure 1) Our study suggests that these PTA molecules are highly structured in solution and can be used to identify protein ligands. We believe that these molecules can be a future source of high-affinity protein ligands. Here we describe the synthetic method combining the power of both split-and-pool and sub-monomer strategies to synthesize a sample one-bead one-compound (OBOC) library of PTAs.
Topics: Amides; Methylation; Peptide Library; Peptides; Peptidomimetics
PubMed: 24998250
DOI: 10.3791/51299 -
Brazilian Journal of Medical and... May 2000This article reports on the design and characteristics of substrate mimetics in protease-catalyzed reactions. Firstly, the basis of protease-catalyzed peptide synthesis... (Review)
Review
This article reports on the design and characteristics of substrate mimetics in protease-catalyzed reactions. Firstly, the basis of protease-catalyzed peptide synthesis and the general advantages of substrate mimetics over common acyl donor components are described. The binding behavior of these artificial substrates and the mechanism of catalysis are further discussed on the basis of hydrolysis, acyl transfer, protein-ligand docking, and molecular dynamics studies on the trypsin model. The general validity of the substrate mimetic concept is illustrated by the expansion of this strategy to trypsin-like, glutamic acid-specific, and hydrophobic amino acid-specific proteases. Finally, opportunities for the combination of the substrate mimetic strategy with the chemical solid-phase peptide synthesis and the use of substrate mimetics for non-peptide organic amide synthesis are presented.
Topics: Acyltransferases; Amides; Catalysis; Cysteine Endopeptidases; Endopeptidases; Glutamic Acid; Hydrolysis; Molecular Mimicry; Peptide Biosynthesis; Substrate Specificity; Thrombin; Trypsin
PubMed: 10775878
DOI: 10.1590/s0100-879x2000000500001 -
Viruses Nov 2020Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67%... (Review)
Review
Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67% of the global population under the age of 50 are infected with HSV-1 and 13% have clinically recurrent HSV-2 infections. The most prescribed antiherpetics are nucleoside analogues such as acyclovir, but the emergence of mutants resistant to these drugs and the lack of available vaccines against human HSVs has led to an imminent need for new antivirals. Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses. Moreover, its amidic derivatives valpromide and valnoctamide also share this antiherpetic activity. This review summarizes the current research on the use of VPA and its amidic derivatives as alternatives to traditional antiherpetics in the fight against HSV infections.
Topics: Alphaherpesvirinae; Amides; Animals; Antiviral Agents; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Valproic Acid
PubMed: 33256172
DOI: 10.3390/v12121356 -
Frontiers in Bioscience (Scholar... Jan 2013Aromatic and heterocyclic amines are a major class of chemical mutagens and carcinogens. The toxicity of these compounds is a consequence of their metabolic activation.... (Review)
Review
Aromatic and heterocyclic amines are a major class of chemical mutagens and carcinogens. The toxicity of these compounds is a consequence of their metabolic activation. The best-characterized enzymatic pathways for aromatic amine activation lead to the formation of reactive esters such as N-acetoxyarylamines, which are believed to be precursors of short-lived nitrenium ions. In the 1960s, nitrenium ions were invoked as likely intermediates in the formation of arylamine-derived DNA adducts. More recently, nitrenium ion chemistry has been studied by methods such as trapping with azide ion, laser flash photolysis, and the preparation of highly stabilized of examples (e.g., dianisylnitrenium ion). In this review, we discuss the development of our understanding of nitrenium ion chemistry, with emphasis on their generation in biological systems and their reactions with critical targets such as DNA.
Topics: Amides; Amines; Aniline Compounds; Carcinogens; Humans
PubMed: 23277055
DOI: 10.2741/s376 -
Molecules (Basel, Switzerland) Aug 2020Peptides represent an important class of biologically active molecules with high potential for the development of diagnostic and therapeutic agents due to their... (Review)
Review
Peptides represent an important class of biologically active molecules with high potential for the development of diagnostic and therapeutic agents due to their structural diversity, favourable pharmacokinetic properties, and synthetic availability. However, the widespread use of peptides and conjugates thereof in clinical applications can be hampered by their low stability in vivo due to rapid degradation by endogenous proteases. A promising approach to circumvent this potential limitation includes the substitution of metabolically labile amide bonds in the peptide backbone by stable isosteric amide bond mimetics. In this review, we focus on the incorporation of 1,4-disubstituted 1,2,3-triazoles as amide bond surrogates in linear peptides with the aim to increase their stability without impacting their biological function(s). We highlight the properties of this heterocycle as a -amide bond surrogate and summarise approaches for the synthesis of triazole-containing peptidomimetics via the Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC). The impacts of the incorporation of triazoles in the backbone of diverse peptides on their biological properties such as, e.g., blood serum stability and affinity as well as selectivity towards their respective molecular target(s) are discussed.
Topics: Amides; Peptides; Peptidomimetics; Triazoles
PubMed: 32781656
DOI: 10.3390/molecules25163576 -
Bioorganic & Medicinal Chemistry Letters Oct 2010Key studies leading to the discovery and definition of the role of endogenous fatty acid amide signaling molecules are summarized. (Review)
Review
Key studies leading to the discovery and definition of the role of endogenous fatty acid amide signaling molecules are summarized.
Topics: Amides; Animals; Fatty Acids; Humans; Signal Transduction
PubMed: 20817522
DOI: 10.1016/j.bmcl.2010.08.048 -
Chemical Communications (Cambridge,... Jun 2018Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and...
Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and amide-III bands distinguish parallel in-register β-sheets from a β-solenoid. Further, spatially resolved Raman spectra reveal molecular heterogeneity in amyloid structures.
Topics: Amides; Amyloid beta-Peptides; Humans; Particle Size; Protein Conformation; Spectrum Analysis, Raman; Surface Properties
PubMed: 29774336
DOI: 10.1039/c8cc03217c