Total synthesis of (−)-muricatacin

A total synthesis of (−)-muricatacin has been achieved using a commercially available starting material and our furan approach to oxacyclic systems, the proven scope of which is thus broadened.     

Lipoprotein(a) determination in human serum using a nitrilotriacetic acid derivative immunosensing scaffold on disposable electrodes

A novel strategy for the construction of a disposable integrated amperometric immunosensor for the sensitive and rapid determination of lipoprotein(a) (Lp(a)), an important predictor of cardiovascular disease risk, in human serum is reported. The approach uses a sandwich format involving the covalent immobilization of selective capture antibodies (antiLp(a)) on the surface of N-[N _α,N _α-bis(carboxymethyl)-lysine]-12-mercaptododecanamide (HS-NTA)-modified screen-printed carbon electrodes (SPCEs). After a blocking step with skimmed milk, the modified antiLp(a)-SPCEs were incubated with a mixture solution containing the target analyte and a fixed concentration of a specific biotinylated antibody (biotin-antiLp(a)) and a streptavidin-horseradish peroxidase (HRP) (Strep-HRP) conjugate. The amperometric responses of the resulting immunosensor at ?0.10 V (vs an Ag pseudo-reference electrode), upon addition of 3,3′,5,5′-tetramethylbenzidine (TMB) as electron transfer mediator and H₂O₂ as the enzyme substrate, were used to monitor the extent of the immunoreactions. The developed methodology exhibited a wide range of linearity between 0.02 and 10 μg mL^?1, a low detection limit (LOD) of 8 ng mL^?1, and a great selectivity against other serum components. The usefulness of the Lp(a) immunosensor was demonstrated by analyzing spiked serum samples as well as a reference serum containing a certified Lp(a) content. Figure

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Basis sets for the evaluation of van der Waals complex interaction energies: Ne–N2 intermolecular potential and microwave spectrum

In order to obtain efficient basis sets for the evaluation of van der Waals complex intermolecular potentials, we carry out systematic basis set studies. For this, interaction energies at representative geometries on the potential energy surfaces are evaluated using the CCSD(T) correlation method and large polarized LPol‐n and augmented polarization‐consistent aug‐pc‐2 basis sets extended with different sets of midbond functions. On the basis of the root mean square errors calculated with respect to the values for the most accurate potentials available, basis sets are selected for fitting the corresponding interaction energies and getting analytical potentials. In this work, we study the Ne–N₂ van der Waals complex and after the above procedure, the aug‐pc‐2–3321 and the LPol‐ds‐33221 basis set results are fitted. The obtained potentials are characterized by T‐shaped global minima at distances between the Ne atom and the N₂ center of mass of 3.39 Å, with interaction energies of ?49.36 cm^?1 for the aug‐pc‐2–3321 surface and ?50.28 cm^?1 for the LPol‐ds‐33221 surface. Both sets of results are in excellent agreement with the reference surface. To check the potentials further microwave transition frequencies are calculated that agree well with the experimental and the aV5Z‐33221 values. The success of this study suggests that it is feasible to carry out similar accurate calculations of interaction energies and ro‐vibrational spectra at reduced cost for larger complexes than has been possible hitherto. © 2013 Wiley Periodicals, Inc.     

Predicting the Helical Sense of Poly(phenylacetylene)s from their Electron Circular Dichroism Spectra

The calculated ECD spectrum (time‐dependent density functional theory TD‐DFT) for small oligomers of polyphenylacetylenes (PPAs) show a very good match with the experimental spectra of the PPA polymers, particularly with the first Cotton band associated to the helical sense of the internal polyenic backbone. This has been proven with a series of PPAs representative of cis‐cisoidal, cis‐transoidal, compressed and stretched polyene backbones, with identical or opposite internal/external rotational senses and allows the prediction of the helical sense of the internal helix of a PPA directly from its CD spectra.     

Discovery of the Lanthipeptide Curvocidin and Structural Insights into its Trifunctional Synthetase CuvL

Lanthipeptides are ribosomally-synthesized natural products from bacteria featuring stable thioether-crosslinks and various bioactivities. Herein, we report on a new clade of tricyclic class-IV lanthipeptides with curvocidin from Thermomonospora curvata as its first representative. We obtained crystal structures of the corresponding lanthipeptide synthetase CuvL that showed a circular arrangement of its kinase, lyase and cyclase domains, forming a central reaction chamber for the iterative substrate processing involving nine catalytic steps. The combination of experimental data and artificial intelligence-based structural models identified the N-terminal subdomain of the kinase domain as the primary site of substrate recruitment. The ribosomal precursor peptide of curvocidin employs an amphipathic α-helix in its leader region as an anchor to CuvL, while its substrate core shuttles within the central reaction chamber. Our study thus reveals general principles of domain organization and substrate recruitment of class-IV and class-III lanthipeptide synthetases.     

The role of post-translational modifications for learning and memory formation

Learning and memory depend on molecular mechanisms involving the protein machinery. Recent evidence proposes that post-translational modifications (PTMs) play a major role in these cognitive processes. PTMs including phosphorylation of serine, threonine, and tyrosine are already well-documented to play a role for synaptic plasticity of the brain, neurotransmitter release, vesicle trafficking and synaptosomal or synaptosomal-associated proteins are substrates of a series of specific protein kinases and their counterparts, protein phosphatases. But protein phosphorylation is only one out of many possible PTMs and first work shows a role of palmitoylation as well as glycosylation for proteins involved in memory formation. Recent technology may now allow reliable detection and even quantification of PTMs of proteins involved in the cognitive system. This will contribute to the understanding of mechanisms for learning and memory formation at the chemical level and has to complement determination of protein levels and indeed determination of protein expression per se generates limited information. The many other PTMs expected including protein nitrosylation and alkylation will even represent targets for pharmacological interventions but in turn increase the complexity of the system. Nevertheless, determination of the presence and the function of PTMs is mandatory and promising cognitive research at the protein chemical level.