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Nature Communications Jan 2022Amides are one of the most fundamental chemical bonds in nature. In addition to proteins and other metabolites, many valuable synthetic products comprise amide bonds....
Amides are one of the most fundamental chemical bonds in nature. In addition to proteins and other metabolites, many valuable synthetic products comprise amide bonds. Despite this, there is a need for more sustainable amide synthesis. Herein, we report an integrated next generation multi-catalytic system, merging nitrile hydratase enzymes with a Cu-catalysed N-arylation reaction in a single reaction vessel, for the construction of ubiquitous amide bonds. This synergistic one-pot combination of chemo- and biocatalysis provides an amide bond disconnection to precursors, that are orthogonal to those in classical amide synthesis, obviating the need for protecting groups and delivering amides in a manner unachievable using existing catalytic regimes. Our integrated approach also affords broad scope, very high (molar) substrate loading, and has excellent functional group tolerance, telescoping routes to natural product derivatives, drug molecules, and challenging chiral amides under environmentally friendly conditions at scale.
Topics: Amides; Biocatalysis; Enzymes; Kinetics; Nitriles; Stereoisomerism
PubMed: 35046426
DOI: 10.1038/s41467-022-28005-4 -
International Journal of Molecular... Feb 2023Amyloid fibril causes serious amyloidosis such as neurodegenerative diseases. The structure is composed of rigid β-sheet stacking conformation which makes it hard to... (Review)
Review
Amyloid fibril causes serious amyloidosis such as neurodegenerative diseases. The structure is composed of rigid β-sheet stacking conformation which makes it hard to disassemble the fibril state without denaturants. Infrared free electron laser (IR-FEL) is an intense picosecond pulsed laser that is oscillated through a linear accelerator, and the oscillation wavelengths are tunable from 3 μm to 100 μm. Many biological and organic compounds can be structurally altered by the mode-selective vibrational excitations due to the wavelength variability and the high-power oscillation energy (10-50 mJ/cm). We have found that several different kinds of amyloid fibrils in amino acid sequences were commonly disassembled by the irradiation tuned to amide I (6.1-6.2 μm) where the abundance of β-sheet decreased while that of α-helix increased by the vibrational excitation of amide bonds. In this review, we would like to introduce the IR-FEL oscillation system briefly and describe combination studies of experiments and molecular dynamics simulations on disassembling amyloid fibrils of a short peptide (GNNQQNY) from yeast prion and 11-residue peptide (NFLNCYVSGFH) from β2-microglobulin as representative models. Finally, possible applications of IR-FEL for amyloid research can be proposed as a future outlook.
Topics: Amyloid; Electrons; Peptides; Amides; Lasers
PubMed: 36835098
DOI: 10.3390/ijms24043686 -
Molecules (Basel, Switzerland) Jan 2019Bridged lactams represent the most effective and wide-ranging method of constraining the amide bond in a non-planar conformation. A previous comprehensive review on this... (Review)
Review
Bridged lactams represent the most effective and wide-ranging method of constraining the amide bond in a non-planar conformation. A previous comprehensive review on this topic was published in 2013 ( , , 5701⁻5765). In the present review, which is published as a part of the , we present an overview of the recent developments in the field of bridged lactams that have taken place in the last five years and present a critical assessment of the current status of bridged lactams in synthetic and physical organic chemistry. This review covers the period from 2014 until the end of 2018 and is intended as an update to , , 5701⁻5765. In addition to bridged lactams, the review covers recent advances in the chemistry of bridged sultams, bridged enamines and related non-planar structures.
Topics: Amides; Biological Products; Lactams; Models, Chemical
PubMed: 30642094
DOI: 10.3390/molecules24020274 -
Molecules (Basel, Switzerland) Dec 2022Acyl moiety is a common structural unit in organic molecules, thus acylation methods have been widely explored to construct various functional compounds. While the... (Review)
Review
Acyl moiety is a common structural unit in organic molecules, thus acylation methods have been widely explored to construct various functional compounds. While the traditional Friedel-Crafts acylation processes work to allow viable construction of arylketones under harsh acid conditions, recent progress on developing acylation methods focused on the new reactivity discovery by exploiting versatile and easily accessible acylating reagents. Of them, alcohols are cheap, have low toxicity, and are naturally abundant feedstocks; thus, they were recently used as ideal acyl precursors in molecule synthesis for ketones, esters, amides, etc. In this review, we display and discuss recent advances in employing alcohols as unusual acyl sources to form C-C and C-heteroatom bonds, with emphasis on the substrate scope, limitations, and mechanism.
Topics: Alcohols; Amides; Acylation; Ketones; Esters
PubMed: 36558110
DOI: 10.3390/molecules27248977 -
Journal of Oleo Science 2012Two long-chain amidoamine derivatives (C13A2AOH and C17A2AOH) bearing three amide moieties were synthesized and their gelation ability and pH responsivity were compared...
Two long-chain amidoamine derivatives (C13A2AOH and C17A2AOH) bearing three amide moieties were synthesized and their gelation ability and pH responsivity were compared with a similar, previously reported amidoamine derivative gelator with two amide moieties. C13A2AOH and C17A2AOH gels prepared in water and organic solvents acted as ambidextrous low molecular mass gelators. X-ray diffraction and Fourier transform infrared spectroscopy analyses revealed that C13A2AOH and C17A2AOH formed lamellar-like aggregates in the gels, where the amide moieties were in a strong intermolecular hydrogen-bonding state. The gelation ability, i.e., the molar ratio of solvent to gelator, was significantly dependent on the length of the alkyl chain and the number of amide moieties. In addition, the C13A2AOH and C17A2AOH hydrogels exhibited highly pH-responsive gel-sol transitions. The gel-sol transition for the hydrogels was induced by protonation of the ternary amine and the transition was completely reversible by regulating only the pH without heating.
Topics: Amides; Hot Temperature; Hydrogels; Hydrogen-Ion Concentration; Molecular Structure; Particle Size; Phase Transition; Surface Properties
PubMed: 23196871
DOI: 10.5650/jos.61.707 -
Molecules (Basel, Switzerland) Oct 2018This review describes how resonance in amides is greatly affected upon substitution at nitrogen by two electronegative atoms. Nitrogen becomes strongly pyramidal and... (Review)
Review
This review describes how resonance in amides is greatly affected upon substitution at nitrogen by two electronegative atoms. Nitrogen becomes strongly pyramidal and resonance stabilisation, evaluated computationally, can be reduced to as little as 50% that of ,-dimethylacetamide. However, this occurs without significant twisting about the amide bond, which is borne out both experimentally and theoretically. In certain configurations, reduced resonance and pronounced anomeric effects between heteroatom substituents are instrumental in driving the HERON (Heteroatom Rearrangement On Nitrogen) reaction, in which the more electronegative atom migrates from nitrogen to the carbonyl carbon in concert with heterolysis of the amide bond, to generate acyl derivatives and heteroatom-substituted nitrenes. In other cases the anomeric effect facilitates S1 and S2 reactivity at the amide nitrogen.
Topics: Acetamides; Amides; Carbon; Nitrogen; Vibration
PubMed: 30384496
DOI: 10.3390/molecules23112834 -
Molecules (Basel, Switzerland) Sep 2022We used two-dimensional infrared spectroscopy to disentangle the broad infrared band in the amide II vibrational regions of native silk films, identifying the single...
We used two-dimensional infrared spectroscopy to disentangle the broad infrared band in the amide II vibrational regions of native silk films, identifying the single amide II modes and correlating them to specific secondary structure. Amide I and amide II modes have a strong vibrational coupling, which manifests as cross-peaks in 2D infrared spectra with frequencies determined by both the amide I and amide II frequencies of the same secondary structure. By cross referencing with well-known amide I assignments, we determined that the amide II (N-H) absorbs at around 1552 and at 1530 cm for helical and β-sheet structures, respectively. We also observed a peak at 1517 cm that could not be easily assigned to an amide II mode, and instead we tentatively assigned it to a Tyrosine sidechain. These results stand in contrast with previous findings from linear infrared spectroscopy, highlighting the ability of multidimensional spectroscopy for untangling convoluted spectra, and suggesting the need for caution when assigning silk amide II spectra.
Topics: Amides; Animals; Bombyx; Silk; Spectrophotometry, Infrared; Tyrosine; Vibration
PubMed: 36234809
DOI: 10.3390/molecules27196275 -
Medicina (Kaunas, Lithuania) Jun 2022There is a growing interest regarding the impact of the perioperative period and the application of anesthetic drugs on the recurrence of cancer metastases. Among them,... (Review)
Review
There is a growing interest regarding the impact of the perioperative period and the application of anesthetic drugs on the recurrence of cancer metastases. Among them, the use of amide-type local anesthetics seems promising since in vitro studies and animal models have shown their potential to inhibit the Intercellular Adhesion Molecule 1 (ICAM-1) expression and Src activity, which are clearly implicated in the process of inflammation and cancer metastases. This review emphasizes the potential of amide-type local anesthetics in this context.
Topics: Amides; Anesthetics, Local; Animals; Inflammation; Neoplasms
PubMed: 35888601
DOI: 10.3390/medicina58070882 -
Frontiers in Cellular and Infection... 2023Mycobacteria assemble a complex cell wall with cross-linked peptidoglycan (PG) which plays an essential role in maintenance of cell wall integrity and tolerance to...
INTRODUCTION
Mycobacteria assemble a complex cell wall with cross-linked peptidoglycan (PG) which plays an essential role in maintenance of cell wall integrity and tolerance to osmotic pressure. We previously demonstrated that various hydrolytic enzymes are required to remodel PG during essential processes such as cell elongation and septal hydrolysis. Here, we explore the chemistry associated with PG cross-linking, specifically the requirement for amidation of the D-glutamate residue found in PG precursors.
METHODS
Synthetic fluorescent probes were used to assess PG remodelling dynamics in live bacteria. Fluorescence microscopy was used to assess protein localization in live bacteria and CRISPR-interference was used to construct targeted gene knockdown strains. Time-lapse microscopy was used to assess bacterial growth. Western blotting was used to assess protein phosphorylation.
RESULTS AND DISCUSSION
In , we confirmed the essentiality for D-glutamate amidation in PG biosynthesis by labelling cells with synthetic fluorescent PG probes carrying amidation modifications. We also used CRISPRi targeted knockdown of genes encoding the MurT-GatD complex, previously implicated in D-glutamate amidation, and demonstrated that these genes are essential for mycobacterial growth. We show that MurT-rseGFP co-localizes with mRFP-GatD at the cell poles and septum, which are the sites of cell wall synthesis in mycobacteria. Furthermore, time-lapse microscopic analysis of MurT-rseGFP localization, in fluorescent D-amino acid (FDAA)-labelled mycobacterial cells during growth, demonstrated co-localization with maturing PG, suggestive of a role for PG amidation during PG remodelling and repair. Depletion of MurT and GatD caused reduced PG cross-linking and increased sensitivity to lysozyme and β-lactam antibiotics. Cell growth inhibition was found to be the result of a shutdown of PG biosynthesis mediated by the serine/threonine protein kinase B (PknB) which senses uncross-linked PG. Collectively, these data demonstrate the essentiality of D-glutamate amidation in mycobacterial PG precursors and highlight the MurT-GatD complex as a novel drug target.
Topics: Amides; Glutamic Acid; Mycobacterium smegmatis; Cell Wall; Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor; Bacterial Proteins; Peptidoglycan
PubMed: 37692163
DOI: 10.3389/fcimb.2023.1205829 -
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