NMR Structure and CD Titration with Metal Cations of Human Prion α2-Helix-Related Peptides

The 173–195 segment corresponding to the helix 2 of the C-globular prion protein domain could be one of several “spots” of intrinsic conformational flexibility. In fact, it possesses chameleon conformational behaviour and gathers several disease-associated point mutations. We have performed spectroscopic studies on the wild-type fragment 173–195 and on its D178N mutant dissolved in trifluoroethanol to mimic the in vivo system, both in the presence and in the absence of metal cations. NMR data showed that the structure of the D178N mutant is characterized by two short helices separated by a kink, whereas the wild-type peptide is fully helical. Both peptides retained these structural organizations, as monitored by CD, in the presence of metal cations. NMR spectra were however not in favour of the formation of definite ion-peptide complexes. This agrees with previous evidence that other regions of the prion protein are likely the natural target of metal cation binding

Reactivity of S- or Se- containing model peptides with environmental relevant Hg ions: LC-MS/MS study

Selenium (Se) is an essential element being present in the form of the naturally occurring amino acid selenocysteine (Sec), 25 human proteins involved in different cellular pathways contain Sec. As the most potent intracellular soft Lewis base, selenocysteine (SeCys) is able to bind electron poor soft acids as heavy metals, of awareness for environmental and human toxicology, Hg ions bind Se by means of higher equilibrium constants than sulfur (ca. 106 times), therefore these values compensate the lower cellular abundance (105 times) of selenols compared to thiols[2]. In this communication we present a comparative reactivity study of Hg(I) and Hg(II) compounds with model peptides: vasopressin (AVP) hormone with antidiuretic and vasopressor actions and its Sec containing analogs. These peptides were synthesized either by standard solid phase peptide Fmoc or Boc protocols. The metal ion interaction with these peptides was investigated by RP- LC coupled with electrospray MS/MS detection (LC-MS/MS). We observed mono, bis and bridged peptide metallations as detailed in the Scheme. Taking into consideration the stability of Se-Hg bonds, our results support the hypothesis of a binding preference of Hg to Sec residues in selenoproteins

Silver (I) N-Heterocyclic Carbene Complexes: A Winning and Broad Spectrum of Antimicrobial Properties

The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics. N-Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC-carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC-Ag neutral and bis NHC-Ag cationic complexes. Their inhibitor effect on bacterial strains Gram-negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms

The financial gap for women in the MENA region: a systemic perspective

Access to finance and financial capability are both intermediate outcomes and components of financial inclusion. Being strictly related to one another, efforts to simply improve financial access without improving financial capability and contextual conditions for development at the same time, will be inadequate. They will be also unsustainable taking into account that choosing and using the most adequate financial product (access) can be complex if not impossible as understanding the full implications in terms of risks, costs and benefits without the skills and knowledge to make informed financial choices (capability) (United Nations, 2009; United Nations, 2010; United Nations Development Programme, 2013). Developing financial capability is consequently just one of the intermediate outcomes for financial inclusion (Deb and Kubzansky, 2012) the attainment of which requires a portfolio of diverse customized products and services. Hence, to successfully include the gender dimension into the financial inclusion agenda, innovative modes of accessing financial services have to be tailored for women, and the capability of using these products developed as a component of the same action (Arora-Jonsson, 2014). To enable such changes, a sharp shift should occur at a market level (Del Giudice et al., 2016). Our paper moves from reading the current scenario, with a focus on the MENA (Middle East and North Africa) region, to discussing the required changes to effectively address financial inclusion for woman. Following the introduction, a short description of the methodology approach adopted and a brief analysis of the literature on women’s financial inclusion in order to identify dominant academic opinions and approaches, are provided. A focus on MENA financial markets enables the analysis of women financial gap in these markets and offers a basis for discussion of the issue aimed to a better understanding of the needs of women entrepreneurs’. Subsequently, required change is proposed by means of a systems thinking view, while suggestions and relative limitations aimed at fostering discussion and further research conclude this work

AI technologies & value co-creation in a luxury goods context

The aim of the paper is to contribute to the literature on the conceptualization of technology as an operant resource and the role of Artificial Intelligence (AI) in value co-creation processes. Resource integration and interaction determine such co-creation, however the issue pivots on whether AI is effectively able to co-create value as an operant resource. With an integrated framework based on the Service Science (SS), the Viable Systems Approach (VSA) & the Variety Information Model (VIM), the Authors show how to the various kinds of AI technology corresponds a diverse level of co-creation. Our (conceptual) study, highlights how AI (e.g. chatbot) with its client profiling capacity achieves consonance in a luxury goods context, thus interpreting customer expectations. At the same time, the man-machine virtuous circuit qualifies the shift from AI (a combination of various technologies with cognitive abilities – listening, comprehending, acting, learning and at times speaking – capable of matching human intelligence) to the more potent IA Intelligence Augmentation

Structural characterization of a neurotoxic threonine-rich peptide corresponding to the human prion protein α2-helical 180-195 segment and comparison with full-length α2-helix-derived peptides

cited By 10International audienceThe 173-195 segment corresponding to the helix 2 of the globular PrP domain is a good candidate to be one of the several 'spots' of intrinsic structural flexibility, which might induce local destabilization and concur to protein transformation, leading to aggregation-prone conformations. Here, we report CD and NMR studies on the α2-helix-derived peptide of maximal length (hPrP[180-195]) that is able to exhibit a regular structure different from the prevalently random arrangement of other α2-helix-derived peptides. This peptide, which has previously been shown to be affected by buffer composition via the ion charge density dependence typical of Hofmeister effects, corresponds to the C-terminal sequence of the PrPC full-length α2-helix and includes the highly conserved threonine-rich 188-195 segment. At neutral pH, its conformation is dominated by β-type contributions, which only very strong environmental modifications are able to modify. On TFE addition, an increase of α-helical content can be observed, but a fully helical conformation is only obtained in neat TFE. However, linking of the 173-179 segment, as occurring in wild-type and mutant peptides corresponding to the full-length α2-helix, perturbs these intrinsic structural propensities in a manner that depends on whether the environment is water or TFE. Overall, these results confirm that the 180-195 parental region in hPrPC makes a strong contribution to the chameleon conformational behavior of the segment corresponding to the full-length α2-helix, and could play a role in determining structural rearrangements of the entire globular domain. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd