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International Journal of Molecular... Oct 2022Considering the enormous importance of protein turns as participants in various biological events, such as protein-protein interactions, great efforts have been made to...
Considering the enormous importance of protein turns as participants in various biological events, such as protein-protein interactions, great efforts have been made to develop their conformationally and proteolytically stable mimetics. Ferrocene-1,1'-diamine was previously shown to nucleate the stable turn structures in peptides prepared by conjugation with Ala () and Ala-Pro (). Here, we prepared the homochiral conjugates of ferrocene-1,1'-diamine with l-/d-Phe (), l-/d-Val (), and l-/d-Leu () to investigate (1) whether the organometallic template induces the turn structure upon conjugation with amino acids, and (2) whether the bulky or branched side chains of Phe, Val, and Leu affect hydrogen bonding. Detailed spectroscopic (IR, NMR, CD), X-ray, and DFT studies revealed the presence of two simultaneous 10-membered interstrand hydrogen bonds, i.e., two simultaneous β-turns in goal compounds. A preliminary biological evaluation of d-Leu conjugate showed its modest potential to induce cell cycle arrest in the G0/G1 phase in the HeLa cell line but these results need further investigation.
Topics: Humans; Metallocenes; Hydrogen Bonding; Diamines; HeLa Cells; Crystallography, X-Ray; Stereoisomerism; Dipeptides; Peptides; Amino Acids; Protein Conformation
PubMed: 36293089
DOI: 10.3390/ijms232012233 -
Lipids in Health and Disease Nov 2011To develop effective strategies in cancer chemoprevention, an increased understanding of endogenous biochemical mediators that block metastatic processes is critically...
BACKGROUND
To develop effective strategies in cancer chemoprevention, an increased understanding of endogenous biochemical mediators that block metastatic processes is critically needed. Dietary lipids and non-steroidal anti-inflammatory drugs (NSAIDs) have a published track record of providing protection against gastrointestinal malignancies. In this regard, we examined the effects of membrane plasmalogens and ibuprofen on regulation of cellular levels of diamines, polyamine mediators that are augmented in cancer cells. For these studies we utilized Chinese hamster ovary (CHO) cells and NRel-4 cells, a CHO cell line with defective plasmalogen synthesis.
RESULTS
NRel-4 cells, which possess cellular plasmalogen levels that are 10% of control CHO cells, demonstrated 2- to 3-fold increases in cellular diamine levels. These diamine levels were normalized by plasmalogen replacement and significantly reduced by ibuprofen. In both cases the mechanism of action appears to mainly involve increased diamine efflux via the diamine exporter. The actions of ibuprofen were not stereospecific, supporting previous studies that cyclooxygenase (COX) inhibition is unlikely to be involved in the ability of NSAIDs to reduce intracellular diamine levels.
CONCLUSIONS
Our data demonstrate that ibuprofen, a drug known to reduce the risk of colorectal cancer, reduces cellular diamine levels via augmentation of diamine efflux. Similarly, augmentation of membrane plasmalogens can increase diamine export from control and plasmalogen-deficient cells. These data support the concept that membrane transporter function may be a therapeutic point of intervention for dietary and pharmacological approaches to cancer chemoprevention.
Topics: Amino Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal; CHO Cells; Cadaverine; Cell Membrane; Cricetinae; Fusion Regulatory Protein 1, Heavy Chain; Ibuprofen; Neoplasms; Plasmalogens; Putrescine
PubMed: 22087745
DOI: 10.1186/1476-511X-10-214 -
MicrobiologyOpen Nov 2019Synthetic 1,3-bis(aryloxy)propan-2-amines have been shown in previous studies to possess several biological activities, such as antifungal and antiprotozoal. In the...
Synthetic 1,3-bis(aryloxy)propan-2-amines have been shown in previous studies to possess several biological activities, such as antifungal and antiprotozoal. In the present study, we describe the antibacterial activity of new synthetic 1,3-bis(aryloxy)propan-2-amines against Gram-positive pathogens (Streptococcus pyogenes, Enterococcus faecalis and Staphylococcus aureus) including Methicillin-resistant S. aureus strains. Our compounds showed minimal inhibitory concentrations (MIC) in the range of 2.5-10 μg/ml (5.99-28.58 μM), against different bacterial strains. The minimal bactericidal concentrations found were similar to MIC, suggesting a bactericidal mechanism of action of these compounds. Furthermore, possible molecular targets were suggested by chemical similarity search followed by docking approaches. Our compounds are similar to known ligands targeting the cell division protein FtsZ, Quinolone resistance protein norA and the Enoyl-[acyl-carrier-protein] reductase FabI. Taken together, our data show that synthetic 1,3-bis(aryloxy)propan-2-amines are active against Gram-positive bacteria, including multidrug-resistant strains and can be a promising lead in the development of new antibacterial compounds for the treatment of these infections.
Topics: Anti-Infective Agents; Benzenesulfonates; Diamines; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Microbial Sensitivity Tests; Microbial Viability; Staphylococcus aureus; Streptococcus pyogenes
PubMed: 30773849
DOI: 10.1002/mbo3.814 -
Nucleic Acids Research May 2021SYBR Gold is a commonly used and particularly bright fluorescent DNA stain, however, its chemical structure is unknown and its binding mode to DNA remains controversial....
SYBR Gold is a commonly used and particularly bright fluorescent DNA stain, however, its chemical structure is unknown and its binding mode to DNA remains controversial. Here, we solve the structure of SYBR Gold by NMR and mass spectrometry to be [2-[N-(3-dimethylaminopropyl)-N-propylamino]-4-[2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene]-1-phenyl-quinolinium] and determine its extinction coefficient. We quantitate SYBR Gold binding to DNA using two complementary approaches. First, we use single-molecule magnetic tweezers (MT) to determine the effects of SYBR Gold binding on DNA length and twist. The MT assay reveals systematic lengthening and unwinding of DNA by 19.1° ± 0.7° per molecule upon binding, consistent with intercalation, similar to the related dye SYBR Green I. We complement the MT data with spectroscopic characterization of SYBR Gold. The data are well described by a global binding model for dye concentrations ≤2.5 μM, with parameters that quantitatively agree with the MT results. The fluorescence increases linearly with the number of intercalated SYBR Gold molecules up to dye concentrations of ∼2.5 μM, where quenching and inner filter effects become relevant. In summary, we provide a mechanistic understanding of DNA-SYBR Gold interactions and present practical guidelines for optimal DNA detection and quantitative DNA sensing applications using SYBR Gold.
Topics: Benzothiazoles; DNA; Diamines; Fluorescent Dyes; Molecular Structure; Organic Chemicals; Quinolines
PubMed: 33905507
DOI: 10.1093/nar/gkab265 -
European Journal of Biochemistry Oct 1996A protein reacting with a monoclonal antibody against human placental diamine oxidase was purified from the specific granules of human neutrofil granulocytes using...
A protein reacting with a monoclonal antibody against human placental diamine oxidase was purified from the specific granules of human neutrofil granulocytes using affinity chromatography on aminohexyl-divinylsulfonyl-agarose. The protein had an M(r) determined by SDS/PAGE, corresponding to diamine oxidase, but had other properties which indicated that it might be a different protein. A combination of protein chemical techniques, including N-terminal sequencing, identified the protein as lactoferrin, an iron-containing protein with an M(r) of approximately 800000, a high isoelectric point and ferroxidase activity. Purified commercial lactoferrin was shown to bind to aminohexyl-divinylsulfonyl-agarose, and to be eluted in a heterogenous way from the matrix by amines and salt. Alignment of the sequences of diamine oxidase and lactoferrin showed that they are similar, indicating a common ancestry for these two different classes of metallo-oxidases.
Topics: Amine Oxidase (Copper-Containing); Amines; Amino Acid Sequence; Antibodies, Monoclonal; Blotting, Western; Chromatography, Affinity; Chromatography, Ion Exchange; Diamines; Electrophoresis, Agar Gel; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Humans; Lactoferrin; Molecular Sequence Data; Neutrophils; Placenta; Sepharose; Sequence Alignment; Sequence Analysis
PubMed: 8898921
DOI: 10.1111/j.1432-1033.1996.0303t.x -
Organic Letters Nov 2017An Ugi multicomponent reaction based two-step strategy was applied to generate medium-sized rings. In the first linear expansion phase, a series of diamines reacted with...
An Ugi multicomponent reaction based two-step strategy was applied to generate medium-sized rings. In the first linear expansion phase, a series of diamines reacted with cyclic anhydrides to produce different lengths of terminal synthetic amino acids as the starting material for the second phase. The Ugi-4-center 3-component reaction was utilized to construct complex medium-sized rings (8-11) by the addition of isocyanides and oxo components. This method features mild conditions and a broad substrate scope.
Topics: Amino Acids; Cyanides; Diamines; Macrocyclic Compounds; Molecular Structure
PubMed: 29083197
DOI: 10.1021/acs.orglett.7b03094 -
Organic Letters Aug 2022Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of...
Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of substituted 1,2-diamines. Herein, the rhodium-catalyzed hydroamination of primary and secondary allylic amines using diverse amine nucleophiles, including primary, secondary, acyclic, and cyclic aliphatic amines to access a wide range of unsymmetrical vicinal diamines, is presented. The utility of this methodology is further demonstrated through the rapid synthesis of several bioactive molecules and analogs.
Topics: Amines; Catalysis; Diamines; Rhodium; Stereoisomerism
PubMed: 35862860
DOI: 10.1021/acs.orglett.2c01911 -
Molecules (Basel, Switzerland) Apr 2017Aromatic substitution reactions between 1,3-diaminobenzene and chloronitrobenzofurazan derivatives have never been reported so far. The aim of the current study was to...
Aromatic substitution reactions between 1,3-diaminobenzene and chloronitrobenzofurazan derivatives have never been reported so far. The aim of the current study was to synthesize novel electron-donor and -acceptor architectures of interest in applied fields and to provide new insights on the nucleophilic behavior of 1,3-diaminobenzenes. The reaction of 1,3-dipiperidinyl-, 1,3-dimorpholinyl-, 1,3-dipyrrolidinyl-, or 1,3-dimethylamino-benzene with 7-chloro-4,6-dinitrobenzofuroxan or with a series of chloro-nitrobenzofurazans has been carried out in mild conditions. The partners reactivity has been investigated by monitoring the reaction course through ¹H-NMR spectroscopy. The reaction occurred in a regioselective way, providing in good yields the novel C-C coupling compounds. Indications on the reactivity behavior for the studied nucleophiles have been relieved.
Topics: Benzene Derivatives; Benzofurans; Diamines; Proton-Phosphate Symporters; Quantum Theory
PubMed: 28445410
DOI: 10.3390/molecules22050684 -
Journal of Biosciences 2021Real-time PCR is a widely used technique for quantification of gene expression. However, commercially available kits for real-time PCR are very expensive. The ongoing...
Real-time PCR is a widely used technique for quantification of gene expression. However, commercially available kits for real-time PCR are very expensive. The ongoing coronavirus pandemic has severely hampered the economy in a number of developing countries, resulting in a reduction in available research funding. The fallout of this will result in limiting educational institutes and small enterprises from using cutting edge biological techniques such as real-time PCR. Here, we report a cost-effective approach for preparing and assembling cDNA synthesis and real-time PCR mastermixes with similar efficiencies as commercially available kits. Our results thus demonstrate an alternative to commercially available kits.
Topics: Benzothiazoles; Diamines; Indicators and Reagents; Quinolines; Real-Time Polymerase Chain Reaction
PubMed: 34845993
DOI: 10.1007/s12038-021-00231-w -
International Journal of Molecular... Sep 2019The reaction-based deposition on various surfaces of an all-organic fluorescent coating is reported here, involving autoxidation of 2 mM dopamine in carbonate buffer at...
The reaction-based deposition on various surfaces of an all-organic fluorescent coating is reported here, involving autoxidation of 2 mM dopamine in carbonate buffer at pH 9.0, in the presence of a 1 mM diamine-resorcinol coupler (Bis-Res) prepared from 2,4-dihydroxybenzaldehyde and hexamethylenediamine (HMDA). Spectral analysis of the films coupled with an LC-MS investigation of the yellow fluorescent mixture was compatible with the formation and deposition of HMDA-linked methanobenzofuroazocinone fluorophores. Both the emission properties and hydrophobicity of the film were abated in a reversible manner following exposure to acid vapors. These results provide an entry to efficient and practical fluorescent coating methodologies based on in situ generation and the deposition of wet adhesive, as well as fluorescent materials combining a strongly emitting fluorophore with the film-forming properties of long chain diamines.
Topics: Benzaldehydes; Diamines; Dopamine; Fluorescent Dyes; Hydrophobic and Hydrophilic Interactions; Molecular Structure; Oxidation-Reduction; Surface Properties
PubMed: 31540228
DOI: 10.3390/ijms20184532