Syntheses and anti‐tubercular activity of β‐substituted and α,β‐disubstituted peptidyl β‐aminoboronates and boronic acids

Tuberculosis is still affecting millions of people worldwide, and new resistant strains of Mycobacterium tuberculosis are being found. It is therefore necessary to find new compounds for treatment. In this paper, we report the synthesis and in vitro testing of peptidyl β‐aminoboronic acids and β‐aminoboronates with anti‐tubercular activity. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Derivatization of peptides as quaternary ammonium salts for sensitive detection by ESI‐MS

A series of model peptides in the form of quaternary ammonium salts at the N‐terminus was efficiently prepared by the solid‐phase synthesis. Tandem mass spectrometric analysis of the peptide quaternary ammonium derivatives was shown to provide sequence confirmation and enhanced detection. We designed the 2‐(1,4‐diazabicyclo[2.2.2] octylammonium)acetyl quaternary ammonium group which does not suffer from neutral losses during MS/MS experiments. The presented quaternization of 1,4‐diazabicyclo[2.2.2]octane (DABCO) by iodoacetylated peptides is relatively easy and compatible with standard solid‐phase peptide synthesis. This methodology offers a novel sensitive approach to analyze peptides and other compounds. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Structure–activity relationship study of antioxidative peptides by QSAR modeling: the amino acid next to C‐terminus affects the activity

Screening, isolation and in vitro assays have been used for characterization of antioxidative peptides derived from food proteins, and incompatible deductions of structural characteristics derived from the isolated peptides have been brought forward. However, there is still little information concerning the structure‐activity relationship of antioxidative peptides. QSAR modeling was performed, respectively, on synthetic tripeptides and tetrapeptides related to LLPHH. According to cumulative squared multiple correlation coefficients (R²), cumulative cross‐validation coefficients (Q²) and relative standard deviation for calibration set (RSD_c), two credible models for tripeptide and tetrapeptide databases, respectively, have been built with partial least squares (PLS) regression (R² for models of tripeptide and tetrapeptide are 0.744 and 0.943, Q² are 0.631 and 0.414, and RSD_c are 0.323 and 0.111, respectively). Meanwhile, according to the cumulative multiple correlation coefficient for the predictive set ($R_{\rm {ext}}^{2}$ ) and the relative standard deviation for the predictive set (RSD_p), the predictive ability of the model for tripeptides also is excellent ($R_{\rm {ext}}^{2}$ and RSD_p are 0.719 and 0.450, respectively). Hydrogen bond property and hydrophilicity of the amino acid residue next to the C‐terminus, and the hydrophobicity as well as electronic propertyof the N‐terminus are more significant; meanwhile, the electronic property of the C‐terminus is beneficial for antioxidant activity. The structural characteristics we found are very useful in understanding and predicting the peptide structures responsible for activity and development of functional foods with peptides as active compounds, or antioxidative peptides as alternatives to other antioxidants. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Social context, stress, and plasticity of aging

Positive social contact is an important factor in healthy aging, but our understanding of how social interactions influence senescence is incomplete. As life expectancy continues to increase because of reduced death rates among elderly, the beneficial role of social relationships is emerging as a cross-cutting theme in research on aging and healthspan. There is a need to improve knowledge on how behavior shapes, and is shaped by, the social environment, as well as needs to identify and study biological mechanisms that can translate differences in the social aspects of behavioral efforts, relationships, and stress reactivity (the general physiological and behavioral response-pattern to harmful, dangerous or unpleasant situations) into variation in aging. Honey bees (Apis mellifera) provide a genetic model in sociobiology, behavioral neuroscience, and gerontology that is uniquely sensitive to social exchange. Different behavioral contact between these social insects can shorten or extend lifespan more than 10-fold, and some aspects of their senescence are reversed by social cues that trigger aged individuals to express youthful repertoires of behavior. Here, I summarize how variation in social interactions contributes to this plasticity of aging and explain how beneficial and detrimental roles of social relationships can be traced from environmental and biological effects on honey bee physiology and behavior, to the expression of recovery-related plasticity, stress reactivity, and survival during old age. This system provides intriguing opportunities for research on aging.     

Abacus: a computational tool for extracting and pre-processing spectral count data for label-free quantitative proteomic analysis

We describe Abacus, a computational tool for extracting spectral counts from MS/MS data sets. The program aggregates data from multiple experiments, adjusts spectral counts to accurately account for peptides shared across multiple proteins, and performs common normalization steps. It can also output the spectral count data at the gene level, thus simplifying the integration and comparison between gene and protein expression data. Abacus is compatible with the widely used Trans-Proteomic Pipeline suite of tools and comes with a graphical user interface making it easy to interact with the program. The main aim of Abacus is to streamline the analysis of spectral count data by providing an automated, easy to use solution for extracting this information from proteomic data sets for subsequent, more sophisticated statistical analysis.     

Sequencing cyclic peptides by multistage mass spectrometry

Some of the most effective antibiotics (e.g. Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of MS-based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage MS, and show its advantages over single-stage MS. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria.     

The attack of the phytopathogens and the trumpet solo: Identification of a novel plant antifungal peptide with distinct fold and disulfide bond pattern

Phytopathogens cause economic losses in agribusiness. Plant-derived compounds have been proposed to overcome this problem, including the antimicrobial peptides (AMPs). This paper reports the identification of Ps-AFP1, a novel AMP isolated from the Pisum sativum radicle. Ps-AFP1 was purified and evaluated against phytopathogenic fungi, showing clear effectiveness. In silico analyses were performed, suggesting an unusual fold and disulfide bond pattern. A novel fold and a novel AMP class were here proposed, the αβ-trumpet fold and αβ-trumpet peptides, respectively. The name αβ-trumpet was created due to the peptide's fold, which resembles the musical instrument. The Ps-AFP1 mechanism of action was also proposed. Microscopic analyses revealed that Ps-AFP1 could affect the fungus during the hyphal elongation from spore germination. Furthermore, confocal microscopy performed with Ps-AFP1 labeled with FITC shows that the peptide was localized at high concentration along the fungal cell surface. Due to low cellular disruption rates, it seems that the main target is the fungal cell wall. The binding thermogram and isothermal titration, molecular dynamics and docking analyses were also performed, showing that Ps-AFP1 could bind to chitin producing a stable complex. Data here reported provided novel structural–functional insights into the αβ-trumpet peptide fold.     

Studies on the peptidase activity of transthyretin (TTR)

Transthyretin (TTR) is a plasma protein transporter of thyroxine (T₄) and retinol and also has peptidase activity. In order to characterize TTR peptidase activity we used fluorescence resonance energy transfer (FRET) peptides derived from Abz-KLRSSK-Q-EDDnp and from two portion-mixing libraries as substrates. Most of the susceptible FRET peptides were cleaved at more than one peptide bond, without particular substrate specificity. The more relevant observation was that the peptides containing E or D were cleaved at only one peptide bond and TTR was competitively inhibited by glutathione analog peptide γ-E-A-G-OH that contains two free carboxyl groups. The dependence on ionic interactions of TTR hydrolytic activity was confirmed by the large inhibitory effects of salt and ionic surfactants. TTR was not inhibited by any usual peptidase inhibitors, except by ortho-phenanthroline and EDTA. The mechanism of TTR catalysis was explored by the pH-profile of TTR hydrolytic activity in different temperatures and by proton inventory. The obtained pK and heat of ionization values suggest that a carboxylate and an ammonium group, possibly from a lysine side chain are involved. These results support the recently proposed inducible metalloprotease mechanism for TTR based on its 3D structure in presence of Zn²⁺ and a series of point mutations [Liz et al., Biochem. J 443 (2012) 769–778].