Rapid On-Resin N-Formylation of Peptides as One-Pot Reaction

N-formylation is a common pre- and post-translational modification of the N-terminus or the lysine side chain of peptides and proteins that plays a role in the initiation of immune responses, gene expression, or epigenetics. Despite its high biological relevance, protocols for the chemical N-formylation of synthetic peptides are scarce. The few available methods are elaborate in their execution and the yields are highly sequence-dependent. We present a rapid, easy-to-use one-pot procedure that runs at room temperature and can be used to formylate protected peptides at both the N-terminus and the lysine side chain on the resin in near-quantitative yields. Only insensitive, storage-stable standard chemicals – formic acid, acetic anhydride, pyridine and DMF – are used. Formylation works for both short and long peptides of up to 34 amino acids and over the spectrum of canonical amino acids.     

Synthesis and Structural Characterization of Macrocyclic Plasmin Inhibitors

Two series of macrocyclic plasmin inhibitors with a C-terminal benzylamine group were synthesized. The substitution of the N-terminal phenylsulfonyl group of a previously described inhibitor provided two analogues with sub-nanomolar inhibition constants. Both compounds possess a high selectivity against all other tested trypsin-like serine proteases. Furthermore, a new approach was used to selectively introduce asymmetric linker segments. Two of these compounds inhibit plasmin with K_i values close to 2 nM. For the first time, four crystal structures of these macrocyclic inhibitors could be determined in complex with a Ser195Ala microplasmin mutant. The macrocyclic core segment of the inhibitors binds to the open active site of plasmin without any steric hindrance. This binding mode is incompatible with other trypsin-like serine proteases containing a sterically demanding 99-hairpin loop. The crystal structures obtained experimentally explain the excellent selectivity of this inhibitor type as previously hypothesized.     

Global optimization in property‐based interplant water integration

This article presents a new global optimization method for the interplant water integration based on properties to characterize streams with numerous components. The problem is formulated as an mixed‐integer non‐linear programming (MINLP) model based on a superstructure that involves all possible options of interest (i.e., reuse and recycle in the same and to other plants and a set of shared treatment units). This formulation exhibits multiple local minima, and to overcome this problem, this article proposes effective branching rules in addition to two new reformulations for the upper bound (integer feasible solution) and the lower limit (relaxed solution), which are incorporated into a spatial branch and bound procedure to handle the bilinear terms in the model. The objective consists in finding the configuration with the minimum total annual cost. Results show that the global optimal solution (involving significant reductions in the fresh water consumption) is reached in few iterations and short central processing unit (CPU) time. © 2012 American Institute of Chemical Engineers AIChE J, 59: 813–833, 2013     

Effects of the Use of Pore Formers on Performance of an Anode Supported Solid Oxide Fuel Cell

The effects of amount of pore former used to produce porosity in the anode of an anode supported planar solid oxide fuel cell were examined. The pore-forming material utilized was rice starch. The reduction rate of the anode material was measured by Thermogravimetric analysis to qualitatively characterize the gas transport within the porous anode materials. Fuel cells with varying amounts of porosity produced by using rice starch as a pore former were tested. The performance of the fuel cell was the greatest with an optimum amount of pore former used to create porosity in the anode. This optimum is believed to be related to a trade off between increasing gas diffusion to the active three-phase boundary region of the anode and the loss of performance because of the replacement of active three-phase boundary regions of the anode with porosity.     

Subunit‐Specific Labeling of Ubiquitin Chains by Using Sortase: Insights into the Selectivity of Deubiquitinases

Information embedded in different ubiquitin chains is transduced by proteins with ubiquitin‐binding domains (UBDs) and erased by a set of hydrolytic enzymes referred to as deubiquitinases (DUBs). Understanding the selectivity of UBDs and DUBs is necessary for decoding the functions of different ubiquitin chains. Critical to these efforts is the access to chemically defined ubiquitin chains bearing site‐specific fluorescent labels. One approach toward constructing such molecules involves peptide ligation by sortase (SrtA), a bacterial transpeptidase responsible for covalently attaching cell surface proteins to the cell wall. Here, we demonstrate the utility of SrtA in modifying individual subunits of ubiquitin chains. Using ubiquitin derivatives in which an N‐terminal glycine is unveiled after protease‐mediated digestion, we synthesized ubiquitin dimers, trimers, and tetramers with different isopeptide linkages. SrtA was then used in combination with fluorescent depsipeptide substrates to effect the modification of each subunit in a chain. By constructing branched ubiquitin chains with individual subunits tagged with a fluorophore, we provide evidence that the ubiquitin‐specific protease USP15 prefers ubiquitin trimers but has little preference for a particular isopeptide linkage. Our results emphasize the importance of subunit‐specific labeling of ubiquitin chains when studying how DUBs process these chains.     

Filler Wetting in Miscible ESBR/SSBR Blends and Its Effect on Mechanical Properties

The selective wetting behavior of silica in emulsion styrene butadiene rubber (ESBR)/solution styrene butadiene rubber (SSBR) blends is characterized by the wetting concept, which is further developed for filled blends based on miscible rubbers. It is found that not only the chemical rubber–filler affinity but also the topology of the filler surface significantly influences the selective filler wetting in rubber blends. The nanopore structure of the silica surface has been recognized as the main reason for the difference in the wetting behavior of the branched ESBR molecules and linear SSBR molecules. However, the effect of nanopore structure becomes more significant in the presence of silane. It is discussed that the adsorption of silane on silica surface constricts the nanopore to some extent that hinders effectively the space filling of the nanopores by the branched ESBR molecules but not by the linear SSBR molecules. As a result, in silanized ESBR/SSBR blends the dominant wetting of silica surface by the tightly bonded layer of SSBR molecules causes a low‐energy dissipation in the rubber–filler interphase. That imparts the low rolling resistance to the blends similar to that of a silica‐filled SSBR compound, while the ESBR‐rich matrix warrants the good tensile behavior, i.e., good abrasion and wear resistance of the blends.

     

Highly sensitive electrochemical sensor based on zirconium oxide-decorated gold nanoflakes nanocomposite 2,4-dichlorophenol detection

Journal of Applied Electrochemistry - In this study, a sensitive and selective electrochemical sensor based on a zirconia oxide-decorated gold nanoflake nanocomposite-modified glassy carbon...     

Towards the detection of human papillomavirus infection by a reagentless electrochemical peptide biosensor

In the present work, we report first results about a technology using a conjugated copolymer poly(5-hydroxy-1,4-naphthoquinone-co-5-hydroxy-2-carboxyethyl-1,4-naphthoquinone) acting both as immobilizing and transducing element for reagentless immunosensor, and its application for the detection of HPV infection. It was shown that the reagentless immunosensor was able to detect the interaction between antigenic peptide L1 from HPV-16 major capsid protein, a dominant epitope involved in viral infection as well as in prophylactic vaccine, and the relevant antibody.     

Synthesis and characterization of (co)polymers containing a phosphonate function for use in dental composites

Novel monomers 1a, 1b, in which a phosphonate function is incorporated in both aromatic rings, were synthesized from the addition reaction of tetraisopropyl [2,2′-disulfanyl-5,5′-thiodiphenyl]-1,1′-diphosphonate and diisopropyl (2-sulfanylphenyl)-1-phosphonate with the glycidylmethacrylate. Free radical homo- and copolymerizations of phosphonate monomers containing methacrylate groups were first carried out in bulk and in THF solution. They offered (co)polymers for potential use in dental resins, in high yields and moderate to high inherent viscosities. The components and structure of the (co)polymers were confirmed by FTIR, SEC, ¹H, ³¹P NMR spectra.

Thermal analysis by using differential scanning calorimetry indicated an amorphous structure of the (co)polymers obtained by polymerization in solution. Upon UV-radiation the composite resins have been synthesized by cross-linking reaction.