Sugar-assisted ligation of N-linked glycopeptides with broad sequence tolerance at the ligation junction

A novel method for the synthesis of N-linked glycopeptides using the sugar-assisted ligation strategy from cysteine free peptides is presented. The ligation junction tolerates a variety of amino acids, favoring less hindered amino acids and those with side chains that could serve as a general base in the ligation pathway. Since our approach allows the ligation of difficult junctions, the method could be applied to the synthesis of large peptides by enzymatic removal of the sugar moiety. Alternatively, more complex glycopeptides can be synthesized using glycosyltransferases. Together, this sequence of reactions should be amenable to the synthesis of glycopeptides and glycoproteins and their deglycosylated products.     

Asymmetric synthesis of all-carbon benzylic quaternary stereocenters via Cu-catalyzed conjugate addition of dialkylzinc reagents to 5-(1-arylalkylidene) Meldrum's acids

The asymmetric synthesis of all-carbon benzylic quaternary stereocenters has been successfully achieved through copper-catalyzed addition of dialkylzinc reagents to 5-(1-arylalkylidene) and 5-(dihydroindenylidene) Meldrum's acids in the presence of phosphoramidite ligand. The resulting benzyl-substituted Meldrum's acids and 1,1-disubstituted indanes were obtained in good yields and up to 99% ee. The significance of substituting the position para, meta, and ortho to the electrophilic benzylic center was highlighted. A benzyl Meldrum's acid product was further transformed to a 3,3-disubstituted 1-indanone and a beta,beta-disubstituted pentanoic acid.     

Generalized and Unified Families of Interpolating Subdivision Schemes

We present generalized and unified families of $(2n)$-point and $(2n-1)$-point $p$-ary interpolating subdivision schemes originated from Lagrange polynomial for any integers $n ≥ 2$ and $p ≥ 3$. Almost all existing even-point and odd-point interpolating schemes of lower and higher arity belong to this family of schemes. We also present tensor product version of generalized and unified families of schemes. Moreover, error bounds between limit curves and control polygons of schemes are also calculated. It has been observed that error bounds decrease when complexity of the scheme decrease and vice versa. Furthermore, error bounds decrease with the increase of arity of the schemes. We also observe that in general the continuity of interpolating scheme do not increase by increasing complexity and arity of the scheme.     

Numerical prediction of droplet dynamics in turbulent flow,using the level set method

In the present article, the droplet dynamics in turbulent flow is numerically predicted. The modelling is based on an interfacial marker-level set (IMLS) method, coupled with the Reynolds-averaged Navier–Stokes (RANS) equations to predict the dynamics of turbulent two-phase flow. The governing equations for time-dependent, two-dimensional and incompressible two-phase flow are described in both phases and solved separately using a control volume approach on structured cell-centred collocated grids. The topological changes of the interface are predicted by applying the level set approach. The kinematic and dynamic conditions on the interface separating the two phases are satisfied. The numerical method proposed is validated against a well-known computational fluid dynamics problem. Further, the deformation and breakup of a single droplet either suddenly moved in air or exposed to turbulent stream are numerically investigated. In general, the developed numerical method demonstrates remarkable capability in predicting the characteristics of complex turbulent two-phase flows.     

Space time fractional KdV Burgers equation for dust acoustic shock waves in dusty plasma with non-thermal ions

The KdV–Burgers equation for dust acoustic waves in unmagnetized plasma having electrons, singly charged nonthermal ions, and hot and cold dust species is derived using the reductive perturbation method. The Boltzmann distribution is used for electrons in the presence of the cold(hot) dust viscosity coefficients. The semi-inverse method and Agrawal variational technique are applied to formulate the space–time fractional KdV–Burgers equation which is solved using the fractional sub-equation method. The effect of the fractional parameter on the behavior of the dust acoustic shock waves in the dusty plasma is investigated.     

Rapid End‐Group Modification of Polysaccharides for Biomaterial Applications in Regenerative Medicine

Polysaccharides have emerged as important functional materials because of their unique properties such as biocompatibility, biodegradability, and availability of reactive sites for chemical modifications to optimize their properties. The overwhelming majority of the methods to modify polysaccharides employ random chemical modifications, which often improve certain properties while compromising others. On the other hand, the employed methods for selective modifications often require excess of coupling partners, long reaction times and are limited in their scope and wide applicability. To circumvent these drawbacks, aniline‐catalyzed oxime formation is developed for selective modification of a variety of polysaccharides through their reducing end. Notably, it is found that for efficient oxime formation, different conditions are required depending on the composition of the specific polysaccharide. It is also shown how our strategy can be applied to improve the physical and functional properties of alginate hydrogels, which are widely used in tissue engineering and regenerative medicine applications. While the randomly and selectively modified alginate exhibits similar viscoelastic properties, the latter forms significantly more stable hydrogel and superior cell adhesive and functional properties. Our results show that the developed conjugation reaction is robust and should open new opportunities for preparing polysaccharide‐based functional materials with unique properties.

     

A review on the synthesis of heteroannulated quinolones and their biological activities

Molecular Diversity - The quinoline scaffold has become an important construction motif for the development of new drugs. The quinolones and their heteroannulated derivatives have high importance...     

A luminescent bacterium assay of fusaric acid produced by <Emphasis Type="Italic">Fusarium proliferatum</Emphasis> from banana

Fusarium proliferatum was isolated as a major pathogen causing the Fusarium disease in harvested banana fruit. One of its major compounds, fusaric acid, was identified by high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–ESI–MS). Because the light intensity of the luminescent bacterium Vibrio qinghaiensis sp. Nov. Q67 can be inhibited by fusaric acid, the fusaric acid content of F. proliferatum was assessed and compared by both the HPLC and luminescent bacterium methods. Although both methods afforded almost similar values of fusaric acid, the latter indicated slightly lower content than the former. Czapek medium was more suitable for the growth of F. proliferatum and fusaric acid production than modified Richard medium, with an optimum pH of approximately 7.0. However, no significant (P < 0.05) correlation was obtained between the fusaric acid production and growth of mycelia of F. proliferatum. The study suggests that the bioevaluation by use of the luminescent bacterium was effective in monitoring fusaric acid production by F. proliferatum without expensive equipment.     

Luciferase-transfected colon adenocarcinoma cell line (DLD-1) for use in Orthotopic Xenotransplantation studies

ABSTRACT: BACKGROUND: Renilla Luciferase reporter gene (rLuc) GL4.82 and GL4.13 promoter are key player in transfection, but precise knowledge of its targets in colon cancer remains limited. The aim of this study was to characterize the best transfection technique to produce a stable transfected colon DLD1 (colorectal adenocarcinoma cell line), therefore imaging based approaches were employed. RESULTS: DLD1 cells were transfected with a Plasmid (SV40-RLuc) carrying Renilla luciferase under the control of the SV-40 promoter, by using two different transfection techniques. Cells expressing the required DNA were isolated after antibiotic (Puramycin) selection. Clones of DLD-1/SV40-RLuc were produced using two different techniques (96 well plates and Petri dish) and their florescence intensity was recorded using IVIS machine (Calliper Life Sciences, Hopkinton, USA). Both techniques were characterized with the help of serial dilution technique. Results from this study substantiated that electroporation is the best. As expected, clones varied in their specific luciferase activity along with the dilutions. With the increase in cell concentration increase in intensity of florescence was recorded. CONCLUSIONS: Based on the results we are confident that this transfected cell line DLD-1/SV40-RLuc (colorectal adenocarcinoma cell line) is the best for further Orthotopic Xenotransplantation Studies and in-vivo experiments as well. Investigation shows that DLD1/SV-rLuc cells have gained little bit resistance against both drugs therefore further study is suggested to know the reasons.     

Targeting deubiquitinases enabled by chemical synthesis of proteins

Ubiquitination/ubiquitylation is involved in a wide range of cellular processes in eukaryotes, such as protein degradation and DNA repair. Ubiquitination is a reversible post-translational modification, with the removal of the ubiquitin (Ub) protein being catalyzed by a family of enzymes known as deubiquitinases (DUBs). Approximately 100 DUBs are encoded in the human genome and are involved in a variety of regulatory processes, such as cell-cycle progression, tissue development, and differentiation. DUBs were, moreover, found to be associated with several diseases and as such are emerging as potential therapeutic targets. Several directions have been pursued in the search for lead anti-DUB compounds. However, none of these strategies have delivered inhibitors reaching advanced clinical stages due to several challenges in the discovery process, such as the absence of a highly sensitive and practically available high-throughput screening assay. In this study, we report on the design and preparation of a FRET-based assay for DUBs based on the application of our recent chemical method for the synthesis of Ub bioconjugates. In the assay, the ubiquitinated peptide was specifically labeled with a pair of FRET labels and used to screen a library comprising 1000 compounds against UCH-L3. Such analysis identified a novel and potent inhibitor able to inhibit this DUB in time-dependent manner with k(inact) = 0.065 min(-1) and K(i) = 0.8 μM. Our assay, which was also found suitable for the UCH-L1 enzyme, should assist in the ongoing efforts targeting the various components of the ubiquitin system and studying the role of DUBs in health and disease.