The cell-penetrating peptide TAT(48-60) induces a non-lamellar phase in DMPC membranes.

Cell-penetrating peptides (CPPs) are short polycationic sequences that can translocate into cells without disintegrating the plasma membrane. CPPs are useful tools for delivering cargo, but their molecular mechanism of crossing the lipid bilayer remains unclear. Here we study the interaction of the HIV-derived CPP TAT (48-60) with model membranes by solid-state NMR spectroscopy and electron microscopy. The peptide induces a pronounced isotropic (31)P NMR signal in zwitterionic DMPC, but not in anionic DMPG bilayers. Octaarginine and to a lesser extent octalysine have the same effect, in contrast to other cationic amphiphilic membrane-active peptides. The observed non-lamellar lipid morphology is attributed to specific interactions of polycationic peptides with phosphocholine head groups, rather than to electrostatic interactions. Freeze-fracture electron microscopy indicates that TAT(48-60) induces the formation of rodlike, presumably inverted micelles in DMPC, which may represent intermediates during the translocation across eukaryotic membranes.     

Monofluoroalkene-Isostere as a 19F NMR Label for the Peptide Backbone: Synthesis and Evaluation in Membrane-Bound PGLa and (KIGAKI)3

Solid-state ¹⁹F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the ¹⁹F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI)₃ are representatives of an α-helix and a β-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for ¹⁹F NMR structure analysis.     

Microbial synthesis of gold nanoparticles: Current status and future prospects

Gold nanoparticles have been employed in biomedicine since the last decade because of their unique optical, electrical and photothermal properties. Present review discusses the microbial synthesis, properties and biomedical applications of gold nanoparticles. Different microbial synthesis strategies used so far for obtaining better yield and stability have been described. It also includes different methods used for the characterization and analysis of gold nanoparticles, viz. UV–visible spectroscopy, Fourier transform infrared spectroscopy, X ray diffraction spectroscopy, scanning electron microscopy, ransmission electron microscopy, atomic force microscopy, electron dispersive X ray, X ray photoelectron spectroscopy and cyclic voltametry. The different mechanisms involved in microbial synthesis of gold nanoparticles have been discussed. The information related to applications of microbially synthesized gold nanoparticles and patents on microbial synthesis of gold nanoparticles has been summarized.     

Daily requirements of Fe,Co and Se during infancy

The daily intakes of trace elements by infants showing optimal pattern of growth are used as the basis to estimate the requirements of Fe, Co and Se during infancy. Since milk is the only food and source of nutrition in the first few months of life, the requirements of these elements are calculated from their average concentrations in human milk and the volume of milk required to supply sufficient amount of energy for maintenance and healthy growth of infants. The concentrations of the three elements in human milk were determined, using the technique of neutron activation followed by radiochemical separation.     

An eco-friendly,sustainable, and greener approach to the synthesis of Dihydroquinazolin-4(1H)-ones using a deep eutectic solvent

A safer, greener, and more effective reaction methodology for the synthesis of dihydroquinazolinones (DHQs) has been developed. The deep eutectic solvent (DES) ZnCl₂/urea employed in this study efficiently accelerated the cyclization of 2-aminobenzamide with different aldehydes (aromatic and heteroaromatic) to afford the target scaffolds without the generation of any oxidized product. This method has exhibited remarkable advantages such as quick reaction time, mild reaction conditions, high yield (82%–98%), operational simplicity, and selectivity. The approach was observed to be tolerant to electron-donating and electron-withdrawing functional groups. Green metric parameters (AEf, OE, AE, RME, CE, etc.) determined further aided this greener chemical approach.     

Synthesis of chloro,fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities

Chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones were produced by reacting malononitrile, barbituric acid, and aromatic aldehydes together with a DABCO catalyst in an aqueous one‐pot reaction. This is the first report of these compounds being synthesized with DABCO as a catalyst, which produced the compounds in yields in excess of 90%. The 2,4‐difluoro derivative ( 11 ) was novel. The structures of the synthesized compounds were elucidated by means of ¹H, ¹³C, and 2D NMR spectroscopy. Compound 2 (2‐Cl derivative) had MBC values of <200μM against both Staphylococcus aureus and MRSA, and the 2‐nitro derivative 5 had an MBC of 191μM against the Gram–ve Escherichia coli. The synthesized compounds were also tested for their anticancer activity against a HeLa cell line, where all the compounds showed better activity (IC₅₀ values between 129μM and 340μM) than 5‐fluorouracil, a commonly known anticancer drug.     

Novel glitazones as PPARγ agonists: molecular design,synthesis, glucose uptake activity and 3D QSAR studies

Background

An alarming requirement for finding newer antidiabetic glitazones as agonists to PPARγ are on its utmost need from past few years as the side effects associated with the available drug therapy is dreadful. In this context, herein, we have made an attempt to develop some novel glitazones as PPARγ agonists, by rational and computer aided drug design approach by implementing the principles of bioisosterism. The designed glitazones are scored for similarity with the developed 3D pharmacophore model and subjected for docking studies against PPARγ proteins. Synthesized by adopting appropriate synthetic methodology and evaluated for in vitro cytotoxicity and glucose uptake assay. Illustrations about the molecular design of glitazones, synthesis, analysis, glucose uptake activity and SAR via 3D QSAR studies are reported.

Results

The computationally designed and synthesized ligands such as 2-(4-((substituted phenylimino)methyl)phenoxy)acetic acid derivatives were analysed by IR, ¹H-NMR, ¹³C-NMR and MS-spectral techniques. The synthesized compounds were evaluated for their in vitro cytotoxicity and glucose uptake assay on 3T3-L1 and L6 cells. Further the activity data was used to develop 3D QSAR model to establish structure activity relationships for glucose uptake activity via CoMSIA studies.

Conclusion

The results of pharmacophore, molecular docking study and in vitro evaluation of synthesized compounds were found to be in good correlation. Specifically, CPD03, 07, 08, 18, 19, 21 and 24 are the candidate glitazones exhibited significant glucose uptake activity. 3D-QSAR model revealed the scope for possible further modifications as part of optimisation to find potent anti-diabetic agents.

Open image in new window

     

Optimized protocol for synthesis of cyclic gramicidin S: starting amino acid is key to high yield

[structures: see text] A simple and highly efficient Fmoc solid-phase protocol for synthesizing the antimicrobial decapeptide gramicidin S and various labeled analogues is presented. When preparing the linear precursor peptides (1a-e), a systematic permutation of the starting amino acid within the cyclic sequence gave different yields between 51% and 93%. Also the subsequent step of cyclization gave widely diverging yields between 26% and 74%, depending again on the starting amino acid. The ease of cyclization was found to correlate with the tendency of the respective linear precursor peptide to assume a preorganized conformation, as observed by circular dichroism. The overall yield is thus critically dependent on the starting amino acid and can be raised from 20% to 70% using (D)Phe. The choice of coupling agent and its counterion was found to play only a marginal role. Irrespective of being able to assume a preorganized conformation, none of the linear precursor peptides exhibited any antimicrobial or hemolytic activity. Using the optimized protocol, which involves only simple Fmoc-couplings and requires no intermittent purification steps, several gramicidin S analogues (3-8) containing 19F-labeled phenylglycine derivatives and/or 15N-labeled amino acids were synthesized for solid-state NMR structure analysis.     

Synthesis of novel pyrazole‐based triazolidin‐3‐one derivatives by using ZnO/ZrO2 as a reusable catalyst under green conditions

An efficient approach for the synthesis of 10 novel pyrazole‐based 1,2,4‐triazolidin‐3‐one derivatives catalyzed by ZnO‐loaded ZrO₂ as heterogeneous catalyst with ethanol as solvent is described. The structure of the mixed metal oxide catalyst was characterized by various instrumental techniques (scanning electron microscopy, transmission electron microscopy, X‐ray diffraction and Brunauer–Emmett–Teller). In smooth reactions, products were accomplished in excellent yields (90–94%) with short reaction times (≈ 45 min). ZnO/ZrO₂ catalyst exhibited good recyclability. The catalyst is reused six times without any noticeable loss of activity. The major advantages of this method are operational simplicity, mild conditions, simple work‐up procedure and broad functional group tolerance.     

Isolation and characterization of flavonoids from the roots of medicinal plant Tadehagi triquetrum (L.) H.Ohashi

Abstract

Three flavonoid compounds were isolated from the roots of medicinal plant Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae). On the basis of the chemical and spectral analysis, the compounds were identified as baicalein (Flavone), naringin and neohesperidin (Flavonone). To the best of our knowledge and based on the literature survey all three compounds were first time reported from this medicinal plant.