Methods development for Analysis of Partially Deglycosylated Proteins and Application to an HIV Envelope Protein Vaccine Candidate

The work presented herein describes the first comprehensive analysis of a partially deglycosylated HIV vaccine candidate envelope protein (Env). The Env, JRFL gp140 ΔCF, with 27 potential glycosylation sites, was partially deglycosylated with PNGase F as part of a strategy to generate a more immunogenic HIV vaccine, and the resulting protein's glycosylation was characterized in a unique workflow using two different glycosidases, Endo H and Endo F3. This unique analysis protocol provided for coverage on 26 of the 27 glycosylation sites, and the data showed that the biochemical treatment with PNGase F resulted in a highly heterogeneous glycoprotein product that had been partially deglycosylated at most of the glycosylation sites. The protocols described in this work could be useful for characterizing the glycosylation site occupancy of other native or biochemically deglycosylated proteins.     

Cocrystallization Tailoring Multiple Radiative Decay Pathways for Amplified Spontaneous Emission

Amplified spontaneous emission (ASE) is intrinsically associated with lasing applications. Inefficient photon energy transfer to ASE is a long‐standing issue for organic semiconductors that consist of multiple competing radiative decay pathways, far from being rationally regulated from the perspective of molecular arrangements. Herein, we achieve controllable molecular packing motifs by halogen‐bonded cocrystallization, leading to ten times increased radiative decay rate, four times larger ASE radiative decay selectivity and thus remarkable ASE threshold decrease from 223 to 22 μJ cm^?2, albeit with a low photoluminescence quantum yield. We have made an in‐depth investigation on the relationship among molecular arrangements, vibration modes, radiative decay profiles and ASE properties. The results suggest that cocrystallization presents a powerful approach to tailor the radiative decay pathways, which is fundamentally important to the development of organic ASE and lasing materials.     

Decoration of Few-Layer Graphene-Like MoS2 and MoSe2 by Noble Metal Nanoparticles

Graphene has been decorated by nanoparticles of noble metals and other inorganic materials. In the present study, we have decorated graphene-like MoS₂ and MoSe₂, containing 3–5 layers, with Au, Ag and Pt nanoparticles. We have characterized these nanocomposites using X-ray diffraction, electron microscopy and absorption spectroscopy. The studies reveal that the surfaces of the layered inorganic materials get uniformly coated with the noble metal nanoparticles. There are indications that the interaction of the metal particles with these layered materials is rather weak.     

Substituent Effect Parameters: Extending the Applications to Organometallic Chemistry

Typically, metal complexes are constituted of an acceptor metal ion and one or more Iigands containing the donor atoms. Accordingly, the properties of a metal complex are equally dependent on the nature of the metal ion and the ligands. Minute structural variations in the ligand will may result in linear changes in the respective energetic parameters and such linear relationships have paramount importance in organometallic chemistry. The variation in ligands is virtually limitless and substantial because of the extent of organic chemistry available for the modelling of desirable ligands, apart from the variation in metal ions. Anyhow, there is still a need for new parameters for the design and quantification of new ligands which in turn leads to the synthesis of metal complexes with possibly predictable chemical properties. Previous studies have demonstrated that quantum chemically derived molecular electrostatic potential (MESP) parameters can be listed as one of the superior quantifiers in this regard, which can act as an effective ligand electronic parameter. The interaction between the ligand part and metal-containing part will be crucial in assessing the reactivity of organometallic complexes. Here we are applying MESP based substituent constants derived from substituted benzenes to forecast the interaction energies in (pyr^*)W(CO)₅, (NHC^*)Mo(CO)₅ and (η⁶-arene^*)Cr(CO)₃ complexes. Ligands and metal ions are varied in each case for better understanding and transparency.     

Synthesis and thermal behaviour of salicylaldimine-based liquid crystalline symmetrical dimers

A series of symmetrical dimers consisting of salicylaldimine moieties connected by flexible alkylene central spacer via ether linkages has been synthesized. In order to validate the empirical rule suggested by Date et al. to account for the smectic behaviour of such dimers, the chain length of the terminal alkoxy chain has been kept constant (C₈) while the number of methylene units in the central spacer was varied from C₃ to C₁₁. Another aim of the present investigation was to understand structure-property relationship in these dimers in which the salicylaldimine mesogenic segment has been used for the first time in dimers. The mesomorphic behaviour of these dimers was evaluated using optical microscopy and differential scanning calorimetry and the structure of some of the mesophases has been further investigated with the help of X-ray diffraction. Our studies reveal that the dimers consisting of 3 to 8 methylene units in the flexible spacer show only smectic (smectic C and smectic A) phases. For the dimers containing 4, 6 and 8 methylene units in the central spacer, a unique filament growth pattern has been observed in the smectic A phase while cooling from the isotropic phase. The dimers containing of C₉ to C₁₁ methylene groups exhibit the nematic phase in addition to smectic modifications. This observation indicates that when the terminal chains are shorter than the spacer, the tendency to form smectic phases is not fully extinguished but is perhaps reduced.     

5-Phenylpyridazinones-A serendipitous route from coumarins

A new route of the ring transformation has been discovered during the reaction of 4-bromomethylcoumarins with hydrazine hydrate leading to the formation of pharmacologically important pyridazinones in a single step with very high yields. These so obtained pyridazinones have the potential for further functional group interconversions.     

A Stochastic Bottleneck Transportation Problem

In this paper, a stochastic bottleneck transportation problem, which aims at minimizing the transportation time target subject to a chance constraint, is formulated and an algorithm based on a parametric programming approach is developed to solve it. Further, assuming the transportation costs to be deterministic, a trade-off analysis between the transportation time target and the total cost is given. In addition, methods are developed which give the whole spectrum of optimal solutions to the problems mentioned above. The algorithms are illustrated by numerical examples. The computational complexity of the algorithms is also discussed.     

ROS Dependent Antifungal and Anticancer Modulations of Piper colubrinum Osmotin

Osmotin, a plant defense protein, has functional similarity to adiponectin, an insulin sensitizingsensitising hormone secreted by adipocytes. We speculated that Piper colubrinum Osmotin (PcOSM) could have functional roles in obesity-related cancers, especially breast cancer. Immunofluorescence assays, flow cytometry, cell cycle analysis and a senescence assay were employed to delineate the activity in MDAMB231 breast cancer cell line. PcOSM pre-treated P. nigrum leaves showed significant reduction in disease symptoms correlated with high ROS production. In silico analysis predicted that PcOSM has higher binding efficiency with adiponectin receptor compared to adiponectin. PcOSM was effectively taken up by MDAMB231 cancer cells which resulted in marked increase in intracellular ROS levels leading to senescence and cell cycle arrest in G2/M stage. This study provides evidence on the ROS mediated direct inhibitory activity of the plant derived osmotin protein on the phytopathogen Phytophthora capsici, and the additional functional roles of this plant defense protein on cancer cells through inducing ROS associated senescence. The strong leads produced from this study could be pursued further to obtain more insights into the therapeutic potential of osmotin in human cancers.