Characterization of Nα-Fmoc-protected dipeptide isomers by electrospray ionization tandem mass spectrometry (ESI-MS(n)): effect of protecting group on fragmentation of dipeptides

A series of positional isomeric pairs of Fmoc-protected dipeptides, Fmoc-Gly-Xxx-OY/Fmoc-Xxx-Gly-OY (Xxx=Ala, Val, Leu, Phe) and Fmoc-Ala-Xxx-OY/Fmoc-Xxx-Ala-OY (Xxx=Leu, Phe) (Fmoc=[(9-fluorenylmethyl)oxy]carbonyl) and Y=CH(3)/H), have been characterized and differentiated by both positive and negative ion electrospray ionization ion-trap tandem mass spectrometry (ESI-IT-MS(n)). In contrast to the behavior of reported unprotected dipeptide isomers which mainly produce y(1)(+) and/or a(1)(+) ions, the protonated Fmoc-Xxx-Gly-OY, Fmoc-Ala-Xxx-OY and Fmoc-Xxx-Ala-OY yield significant b(1)(+) ions. These ions are formed, presumably with stable protonated aziridinone structures. However, the peptides with Gly- at the N-terminus do not form b(1)(+) ions. The [M+H](+) ions of all the peptides undergo a McLafferty-type rearrangement followed by loss of CO(2) to form [M+H-Fmoc+H](+). The MS(3) collision-induced dissociation (CID) of these ions helps distinguish the pairs of isomeric dipeptides studied in this work. Further, negative ion MS(3) CID has also been found to be useful for differentiating these isomeric peptide acids. The MS(3) of [M-H-Fmoc+H](-) of isomeric peptide acids produce c(1)(-), z(1)(-) and y(1)(-) ions. Thus the present study of Fmoc-protected peptides provides additional information on mass spectral characterization of the dipeptides and distinguishes the positional isomers.     

Differentiation of Positional Isomers of Hybrid Peptides Containing Repeats of β-Nucleoside Derived Amino Acid (β-Nda-) and L-Amino Acids by Positive and Negative Ion Electrospray Ionization Tandem Mass Spectrometry (ESI-MS<Superscript><Emphasis Type="Italic">n</Emphasis></Superscript>)

A new class of positional isomeric pairs of -Boc protected oligopeptides comprised of alternating nucleoside derived β-amino acid (β-Nda-) and L-amino acid residues (alanine, valine, and phenylalanine) have been differentiated by both positive and negative ion electrospray ionization ion-trap tandem mass spectrometry (ESI-MS ⁿ ). The protonated dipeptide positional isomers with β-Nda- at the N-terminus lose CH₃OH, NH₃, and C₂H₄O₂, whereas these processes are absent for the peptides with L-amino acids at the N-terminus. Instead, the presence of L-amino acids at the N-terminus results in characteristic retro-Mannich reaction involving elimination of imine. A good correlation has been observed between the conformational structure of the peptides and the abundance of y_n⁺ and b_n⁺ ions in MS ⁿ spectra. In the case of tetrapeptide isomers that are reported to form helical structures in solution phase, no y_n⁺ and b_n⁺ ions are observed when the corresponding amide -NH- participates in the helical structures. In contrast, significant y_n⁺ and b_n⁺ ions are formed when the amide -NH- is not involved in the H-bonding. In the case of tetra- and hexapeptides, it is observed that abundant b_n⁺ ions are formed, presumably with stable oxazolone structures when the C-terminus of the b_n⁺ ions possessed L-amino acid and the β-Nda- at the C-terminus appears to prevent the cyclization process leading to the absence of corresponding b_n⁺ ions.     

Magnetic and electrical properties of oxygen stabilized nickel nanofibers prepared by the borohydride reduction method

Fine nickel fibers have been synthesized by chemical reduction of nickel ions in aqueous medium with sodium borohydride. The thermal stability and relevant properties of these fibers, as-prepared as well as air-annealed, have been investigated by structural, magnetic and electrical measurements. As-prepared samples appear to have a novel crystal structure due to the presence of interstitial oxygen. Upon annealing in air, the fcc-Ni phase emerges out initially and develops into a nanocomposite subsequently by retaining its fiber-like structure in nano phase. The as-prepared sample is observed to be weakly magnetic at room temperature, but attains surprisingly high magnetization values at low temperatures. This is attributed to the modified spin structure, presumably due to the presence of interstitial oxygen in the lattice. Development of a weakly ferromagnetic and electrically conducting phase upon annealing in air is attributed to the formation of the fcc-Ni phase. The structural phase transformations corroborate well with magnetic and electrical measurements.     

PCEP enhances IgA mucosal immune responses in mice following different immunization routes with influenza virus antigens

Background  

We previously demonstrated that polyphosphazenes, particularly PCEP, enhance immune responses in mice immunized subcutaneously and intranasally. The objective of the present study was to investigate the efficacy of polyphosphazenes as adjuvants when delivered through different routes of vaccine administration.     

Molecular organization in liquid crystals: A comparative computational analysis

A comparative computational analysis of molecular organization in four-nematogenic acids (nOCAC) having two, four, six, and eight carbon atoms in the alkyl chain is carried out with respect to translatory and orientational motions. The evaluation of the atomic charge and dipole moment at each atomic center is performed through the complete neglect differential overlap (CNDO/2) method. The Rayleigh-Schrödinger perturbation theory, along with the multicentered-multipole expansion method, is employed to evaluate the long-range interactions, while the “6-exp” potential function is assumed for short-range interactions. The total interaction-energy values obtained through these computations are used to calculate the probability of each configuration at the phase transition temperature via the Maxwell-Boltzmann formula. Further, the flexibility of various configurations is studied in terms of variation of probability due to small departures from the most probable configuration. A comparative picture of molecular parameters, such as the total energy, binding energy, and total dipole moment, is given. An attempt is made to explain the nematogenic behavior of these liquid crystals in terms of their relative order and, thereby, to develop a molecular model for the liquid crystallinity.     

Hierarchical Ultrathin Layered GO-ZnO@CeO2 Nanohybrids for Highly Efficient Methylene Blue Dye Degradation

Highly efficient interfacial contact between components in nanohybrids is a key to achieving great photocatalytic activity in photocatalysts and degradation of organic model pollutants under visible light irradiation. Herein, we report the synthesis of nano-assembly of graphene oxide, zinc oxide and cerium oxide (GO-ZnO@CeO₂) nanohybrids constructed by the hydrothermal method and subsequently annealed at 300 °C for 4 h. The unique graphene oxide sheets, which are anchored with semiconducting materials (ZnO and CeO₂ nanoparticles), act with a significant role in realizing sufficient interfacial contact in the new GO-ZnO@CeO₂ nanohybrids. Consequently, the nano-assembled structure of GO-ZnO@CeO₂ exhibits a greater level (96.66%) of MB dye degradation activity than GO-ZnO nanostructures and CeO₂ nanoparticles on their own. This is due to the thin layers of GO-ZnO@CeO₂ nanohybrids with interfacial contact, suitable band-gap matching and high surface area, preferred for the improvement of photocatalytic performance. Furthermore, this work offers a facile building and cost-effective construction strategy to synthesize the GO-ZnO@CeO₂ nanocatalyst for photocatalytic degradation of organic pollutants with long-term stability and higher efficiency.     

ChemInform Abstract: Towards Detection of a Long‐Lived Protonated Metal Cation: Generation of GeH2+ Using High‐Energy Collisions.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

A pharmacokinetic study to correlate the hypoglycemic effect of phlorizin in rats: Identification of metabolites as inhibitors of sodium/glucose cotransporters

Phlorizin (PRZ) is a natural product that belongs to a class of dihydrochalcones. The unique pharmacological property of PRZ is to block glucose absorption or reabsorption through specific and competitive inhibitors of the sodium/glucose cotransporters (SGLTs) in the intestine (SGLT1) and kidney (SGLT2). This results in glycosuria by inhibiting renal reabsorption of glucose and can be used as an adjuvant treatment for type 2 diabetes. The pharmacokinetic profile, metabolites of the PRZ, and efficacy of metabolites towards SGLTs are unknown. Therefore, the present study on the characterization of hitherto unknown in vivo metabolites of PRZ and pharmacokinetic profiling using liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) and accurate mass measurements is undertaken. Plasma, urine, and feces samples were collected after oral administration of PRZ to Sprague–Dawley rats to identify in vivo metabolites. Furthermore, in silico efficacy of the identified metabolites was evaluated by docking study. PRZ at an intraperitoneal dose of 400 mg/kg showed maximum concentration in the blood to 439.32 ± 8.84 ng/mL at 1 h, while phloretin showed 14.38 ± 0.33 ng/mL at 6 h. The pharmacokinetic profile of PRZ showed that the maximum concentration lies between 1 and 2 h after dosing. Decreased blood glucose levels and maximum excretion of glucose in the urine were observed when the PRZ and metabolites were observed in plasma. The identification and characterization of PRZ metabolites by LC/ESI/MS/MS further revealed that the phase I metabolites of PRZ are hydroxy (mono-, di-, and tri-) and reduction. Phase II metabolites are O-methylated, O-acetylated, O-sulfated, and glucuronide metabolites of PRZ. Further docking study revealed that the metabolites diglucuronide metabolite of mono-hydroxylated PRZ and mono-glucuronidation of PRZ could be considered novel inhibitors of SGLT1 and SGLT2, respectively, which show better binding affinities than their parent compound PRZ and the known inhibitors.