Construction of diverse peptide structural architectures via chemoselective peptide ligation

Herein, we report the development of a facile synthetic strategy for constructing diverse peptide structural architectures via chemoselective peptide ligation. The key advancement involved is to utilize the benzofuran moiety as the peptide salicylaldehyde ester surrogate, and Dap–Ser/Lys–Ser dipeptide as the hydroxyl amino functionality, which could be successfully introduced at the side chain of peptides enabling peptide ligation. With this method, the side chain-to-side chain cyclic peptide, branched/bridged peptides, tailed cyclic peptides and multi-cyclic peptides have been designed and successfully synthesized with native peptidic linkages at the ligation sites. This strategy has provided an alternative strategic opportunity for synthetic peptide development. It also serves as an inspiration for the structural design of PPI inhibitors with new modalities.

Methods of introducing peptide salicylaldehyde esters and hydroxyl amine functionality into the peptide side chain have been developed. Diverse peptide structural motifs were constructed via ligation with native amide linkages at the ligation sites.     

X-Ray Structure and Proton NMR Study of a Hexacoordinated Lithium Complex

The structure of the lithium complex with1,3,5-tris[oxymethylene(N,N-dicyclohexyl)carboxyamido]cyclohexanehas been determined by the X-ray method.The compound is triclinic, space group P¯1,a = 15.623(3), b = 19.279(4),c = 19.295(4)Å = 102.32(3), = 92.45(3), = 105.67(3)0, V = 5436(2)Å3, Z = 4. Itscomposition is represented by the formulaC48H82N3O6LiI 0.5H2O. The lithium cationis encapsulated in a polar pseudo-cavity of six oxygen atoms of the ligandmolecule and displays a distorted trigonal prism coordination. The conformationof the ligand in the solid state complex has been compared with the conformationof the complex in solution determined by 1H-NMR measurements.Supplementary data relevant to this publication have been deposited with the British Library, No. SUP 82224 (21 pages).     

The sorption of some radiocations on microporous titanosilicate ETS-10

The microporous titanosilicate ETS-10 synthesized from gel with following molar composition: 1.0 Na₂O: 1.49 SiO₂ : 0.2 TiO₂ : 0.6 KF : 1.28 HCl : 39.5 H₂O was subjected to sorption of radioactive cations ¹¹⁵Cd²⁺, ²⁰⁴Hg²⁺, ⁶⁰Co²⁺ and ¹³⁷Cs⁺ (M) from aqueous solution, in the absence of ionic competition. The uptake of these cations on the ETS-10 was compared by means of the distribution coefficient (K_d) versus contact time and sorption capacity (R) at equilibrium. The FT-IR spectra of M-ETS-10 sorption products exhibit a modification of the absorption band, principally at 381 cm^-1.     

Effects of Y incorporation in TaON gate dielectric on electrical performance of GaAs metal–oxide–semiconductor capacitor

In this study, GaAs metal–oxide–semiconductor (MOS) capacitors using Y‐incorporated TaON as gate dielectric have been investigated. Experimental results show that the sample with a Y/(Y + Ta) atomic ratio of 27.6% exhibits the best device characteristics: high k value (22.9), low interfacestate density (9.0 × 10¹¹ cm^–2 eV^–1), small flatband voltage (1.05 V), small frequency dispersion and low gate leakage current (1.3 × 10^–5A/cm² at V_fb + 1 V). These merits should be attributed to the complementary properties of Y₂O₃ and Ta₂O₅:Y can effectively passivate the large amount of oxygen vacancies in Ta₂O₅, while the positively‐charged oxygen vacancies in Ta₂O₅ are capable of neutralizing the effects of the negative oxide charges in Y₂O₃. This work demonstrates that an appropriate doping of Y content in TaON gate dielectric can effectively improve the electrical performance for GaAs MOS devices.

Capacitance–voltage characteristic of the GaAs MOS capacitor with TaYON gate dielectric (Y content = 27.6%) proposed in this work with the cross sectional structure and dielectric surface morphology as insets.     

High‐efficiency polymer solar cells based on phenylenevinylene copolymer with BF2‐azopyrrole complex and CN‐PC70BM with solvent additive

Power conversion efficiency (PCE) of phenylenevinylene‐based copolymer with BF₂ azopyrrole complex (PB)/modified PC₇₀BM, that is, CN‐PC₇₀BM bulk heterojunction solar cells improves from 2.16 to 4.90% using a processing additive and drying condition. The results demonstrate that a processing additive and drying condition provides an effective means to control both the surface roughness and finer interpenetrating networks to enhance the exciton dissociation into free charge carriers, charge transportation, and collection. Taking into the account of simple device fabrication process without thermal annealing, the PCE of the polymer solar cell can further improved by chloronapthalene (CN) additive under the fast drying condition. The average carrier lifetimes extracted from the impedance spectra and found to correlate with measured PCEs. At short circuit conditions and illumination, the average charge carrier lifetime was found vary from 16.8 to 32 μs with power conversion efficiencies ranging from 3.0 to 4.9%. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

pH‐ and Thiol‐Responsive BODIPY‐Based Photosensitizers for Targeted Photodynamic Therapy

A diiodo distyryl boron dipyrromethene (BODIPY) core was conjugated to two ferrocenyl quenchers through acid‐labile ketal and/or thiol‐cleavable disulfide linkers, of which the fluorescence and photosensitizing properties were significantly quenched through a photoinduced electron‐transfer process. The two symmetrical analogues that contained either the ketal or disulfide linkers could only be activated by a single stimulus, whereas the unsymmetrical analogue was responsive to dual stimuli. Upon interaction with acid and/or dithiothreitol (DTT), these linkers were cleaved selectively. The separation of the BODIPY core and the ferrocenyl moieties restored the photoactivities of the former in phosphate buffered saline and inside the MCF‐7 breast cancer cells, rendering these compounds as potential activable photosensitizers for targeted photodynamic therapy. The dual activable analogue exhibited the greatest enhancement in intracellular fluorescence intensity in both an acidic environment (pH 5) and the presence of DTT (4 mm ). Its photocytotoxicity against MCF‐7 cells also increased by about twofold upon preincubation with 4 mm of DTT. The activation of this compound was also demonstrated in nude mice bearing a HT29 human colorectal carcinoma. A significant increase in fluorescence intensity in the tumor was observed over 9 h after intratumoral injection.     

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.