Role of primary and secondary protein structure in neurotransmitter receptor activation mechanisms

A proton transfer triggered by a ligand interacting with thereceptor had been suggested as the initial step in the activationof a receptor for the neurotransmitter serotonin (5-hydroxy-tryptamine;5-HT). To evaluate the role of the receptor macromolecule inmodulating the primary molecular event in ligand-mediated activation,the process of proton transfer was analysed in the environmentof a protein model for the 5-HT receptor. In the absence ofa detailed receptor structure, the enzyme actinidin was chosenas the model for the receptor based on criteria obtained fromstructure-activity considerations on the ligands. The firstsimulation of a mechanism for receptor activation was performedon this model using methods of theoretical chemistry to studythe effect of specific structural elements. The premise is thatthe role of the elements of secondary structure of soluble proteins(e.g. actinidin) in determining structure-function relationsin these macromolecules is maintained when these elements arepart of membrane-bound receptor proteins. Results from the calculationsof the effects of the six alpha helices of actinidin on theproton transfer process from the imidazolium side chain of His162 to the thiol side chain of Cys 25 in the protein show thatthe helices contribute in different ways to modulate the energyof proton transfer. The largest helix, Al, opposes the protontransfer through the effect of the helix dipole. The chargedresidues (primary structure) in helix A3 favor the proton transfer,and mask the effect of its helix dipole (secondary structure)which opposes the transfer. The direction of the proton transfersimulated for the activation mechanism is opposite to that assumedin the catalytic process of the thiol protease, and the entireprotein environment opposes the transfer. This supports thespecific role of the ligand in triggering the proton transferas a response to its binding.     

Fast and efficient synthesis of high molecular weight poly(epsilon‐caprolactone) diols by microwave‐assisted polymer synthesis

Because of advantageous features such as shorter reaction times, greater yields, limited generation of by‐products and relatively easy and straightforward scale‐up, microwave‐assisted synthesis has become a very appealing tool in organic synthesis. Conversely, its implementation in the context of the synthesis of biomaterials for biopharmaceutical applications has been more limited. The present work reports on the fast and efficient microwave‐assisted synthesis of poly(ethylene glycol) (PEG)‐initiated poly(ε‐caprolactone) diols (PCL) by the ring‐opening polymerization (ROP) of ε‐caprolactone using stannous octanoate as catalyst. Since the PEG content in the synthesized copolymers was extremely low (0.2–1.9%), products were highly hydrophobic and displayed the intrinsic thermal properties of pure PCL. As opposed to the more time‐consuming conventional thermally‐driven synthesis that usually demands 2–3 h, the microwave technique resulted in intermediate to high molecular weight PEG‐PCL derivatives within 10–15 min. The influence of different parameters affecting the synthetic process, namely monomer‐to‐initiator ratio, reaction time, catalyst concentration and the presence, type, and concentration of solvent were thoroughly investigated. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Thermotropic liquid crystalline polymers as protective coatings for aerospace

Liquid crystalline polymers (LCPs) have potential as multifunctional, environmentally friendly coatings for aerospace, overcoming the disadvantages of current materials. Their use, however, has been hindered mainly by their poor adhesion strength. The present work studies novel liquid crystalline thermosetting polymers (LCTs), which can overcome the disadvantages of commercial LCPs for protective coatings in aerospace applications. Phenylethynyl terminated liquid crystalline oligomers based on 4-hydroxybenzoic acid (HBA) and 6-hydroxy-2-naphthoic acid (HNA) were synthesized and melt-pressed on grit-blasted aluminum to obtain 25 μm and 80 μm thick coatings. The presence of coating defects and curing kinetics were investigated, and the adhesion, mechanical properties and environmental resistance were compared with a commercial LCP reference material (Vectra^®). The LCTs showed highly improved adhesion; moreover, fully cured LCTs are harder and stiffer than commercial LCPs, which are expected to increase their wear and impact resistance. The coatings showed no swelling, peeling, or blistering after 500 h of full immersion in fluids such as jet fuel and turbine oil; furthermore, LCTs resisted 1000 h in corrosive fog (salt-spray) and hot moisture. Exposed samples retained their hardness, modulus, and pull-off strength, evidencing the outstanding chemical resistance of these LCTs. Our findings showed the potential of LCTs as protective and wear resistant coatings, particularly in the aggressive environments of aerospace applications. However, results suggest that exposed coating/substrate interfaces constitute paths for environmental attack. Further research aims at elucidating the possible mechanisms.     

Effect of combining ethylene/methyl acrylate/glycidyl methacrylate terpolymer and an organoclay on the toughening of poly(lactic acid)

Blends of poly(lactic acid) (PLA) and ethylene/methyl acrylate/glycidyl methacrylate terpolymer (EMA‐GMA) with and without the addition of an organoclay were prepared by melt mixing in a twin screw extruder. Mechanical, morphological, structural, and rheological properties of the systems have been investigated as function of its compositions. The impact strength (IS) of PLA increased with the addition of EMA‐GMA. Furthermore, the addition of 2.5 wt% of organoclay to the PLA/EMA‐GMA blend promoted improvements in the mechanical properties, such as IS, tensile strength, and strain‐at‐break. Further addition of organoclay, 5 wt%, led to a formation of a double percolated network, where the clay particles form bridges across EMA‐GMA droplets and glue them together, however, without coalescence. In addition, morphological and wide‐angle X‐ray scattering analyses evidenced that the clay presents a partially exfoliated structure and that remains inside the EMA‐GMA droplets, probably as a consequence of the approach used to produce the systems. POLYM. ENG. SCI., 54:1922–1930, 2014. © 2013 Society of Plastics Engineers     

Chitin characterization by SEM,FTIR, XRD,and 13C cross polarization/mass angle spinning NMR

The full characterization of chitin obtained from squid, shrimp, prawn, lobsters, and king crab is reported. Elemental analysis, including metals such as Ca, Mg, Zn, Cd, Hg, Cr, Mn, Cu, and Pb, was performed, which is quite relevant because the skeleton composition is slightly different for each species. The morphology was studied by means of TEM and their compositions were determined by energy‐dispersive X‐ray analysis. ¹³C cross polarization/magic angle spinning NMR was applied to determine the chemical shift of all the carbons and the difference between them. Chitin was isolated by using chemical methods, alternating hydrochloric acid and sodium hydroxide. The α‐chitin from shrimp, prawn, lobsters, and king crabs showed two signals at 73.7 and 75.6 ppm. Meanwhile, the β‐chitin from squid exhibited one signal at 75.2 ppm. FTIR studies were used to analyze α‐chitin from shrimp and β‐chitin from squid. The α‐chitin exhibited amide I vibration modes at 1660 and 1627 cm^?1, whereas the β‐chitin showed one band at 1656 cm^?1. X‐ray diffraction showed that α‐chitin is orthorhombic (a = 4.74 Å, b = 18.86 Å, and c = 10.32 Å) and β‐chitin had a monoclinic dihydrated form (a = 4.80 Å, b = 10.40 Å, c = 11.10 Å, and β = 97°). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1876–1885, 2004     

Removal of N‐methylpyrrolidone hydrogen‐bonded to polyaniline free‐standing films by protonation–deprotonation cycles or thermal heating

Free‐standing films of polyaniline (PANI), in an emeraldine base state, prepared by evaporation of polymer solutions in N‐methylpyrrolidone (NMP) retain solvent even under dynamic vacuum drying as indicated by transmission Fourier transform infrared (FTIR) spectroscopy, where a band at 1670 cm^?1 is clearly observed. Upon protonation–deprotonation cycles in aqueous media the weight of the dry base film decreases indicating gradual loss of NMP. Transmission FTIR spectra shows also the washing out of NMP with a clear decrease in intensity of the hydrogen‐bonded >C?O stretching band (1670 cm^?1) of NMP. During this process the bands between 3500 and 3200 cm^?1, assigned to >N? H stretching in the PANI backbone, change intensity suggesting that intermolecular hydrogen‐bonded >N? H, with carbonyl oxygen of NMP, is replaced by free >N? H. This is clear evidence of specific interaction of NMP with the emeraldine base. A similar loss of NMP is observed during heating but evidence of polymer degradation is also present. A mechanism is proposed to account for the loss of hydrogen‐bonding ability upon protonation which requires delocalization of the radical cations in the protonated films. © 2001 Society of Chemical Industry     

Novel Type II Fatty Acid Biosynthesis (FAS II) Inhibitors as Multistage Antimalarial Agents

Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood‐ and pre‐erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver‐stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood‐stage parasite growth with IC₅₀ values of 1.7 and 3.0 μM and lead to a more prominent developmental attenuation of liver‐stage parasites than the gold‐standard drug, primaquine.     

A simple strategy to generate light-responsive azobenzene-containing epoxy networks

Azobenzene containing epoxy networks are a class of photosensitive materials characterized by high thermal, optical and mechanical stability, promising for reversible optical storage applications. Here, we propose an encouraging two-step method to fabricate crosslinked coatings by simply reacting an amine-functionalized azobenzene and an epoxy resin in bulk for specified times to get soluble products (network precursors). Thin films based on these precursors were prepared, and thermally crosslinked in order to obtain high-T_g materials. The optical response of the materials was determined, both before and after crosslinking. In the case of the samples as prepared, the dynamic time response of the system is fast, as well as the relaxation of the photoinduced birefringence, as expected due to the high mobility of the chromophore. On the other hand, crosslinked systems have a slightly slower response, but higher values of remnant birefringence, providing stability of the photoinduced orientation, what makes them promising materials to use in optical storage applications. Besides, further analysis on the effect of temperature on the induced birefringence of the polymeric networks was also conducted to help optimization of material design. Finally, we had presented some preliminary investigations of surface relief grating recording in the obtained new materials.