In-peptide synthesis of di-oxazolidinone and dehydroamino acid-oxazolidinone motifs as \u3b2-turn inducers

Small and easy-to-do mimetics of \u3b2-turns are of great interest to interfere with protein-protein recognition events mediated by \u3b2-turn recognition motifs. We propose a straightforward procedure for constraining the conformation of tetrapeptides lacking a pre-formed scaffold. According to the stereochemistry array, N-Ts tetrapeptides including Thr or PhSer (phenylserine) at the positions 2 or 3 gave rise in a single step to the sequences Oxd 2-Oxd3 or \u394Abu2-Oxd3 (Oxd, oxazolidin-2-one; \u394Abu, 2,3-dehydro-2-aminobutyric). These pseudo-Pro residues displayed highly constrained, and \u3c7 dihedral angles, and induced clear \u3b2-turns or inverse turns of type I or II, as determined by extensive spectroscopic and computational analyses. \ua9 The Royal Society of Chemistry 2013

Sustainability in peptide chemistry: current synthesis and purification technologies and future challenges.

Developing greener synthesis processes is an inescapable necessity to transform the industrial landscape, mainly in the pharmaceutical sector, into a long-term, sustainable reality. In this context, the renaissance of peptides as medical treatments, and the enforcement of more stringent sustainability requirements by regulatory agencies, pushed chemists toward the introduction of sustainable processes to prepare highly pure, active pharmaceutical ingredients (APIs). Innovative upstream (synthesis) and downstream (purification) methodologies have been developed during the last 5 years with the introduction and optimization of several technologies in solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), chemoenzymatic peptide synthesis (CEPS), and chromatographic procedures. These innovations are also moving toward the introduction of continuous processes that represent one of the most important targets for iterative processes. This overview discusses the most recent efforts in making peptide chemistry greener. The extensive studies that were carried out on green solvents, reaction conditions, auxiliary reagents and purification technologies in the peptide segment can be useful to other fields of organic synthesi

Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics

ESPON Italian evidence in changing Europe

Il volume, che rientra nelle attività dell’ESPON Contact Point Italia, accoglie i risultati del contributo dei Partner Italiani allo sviluppo dei progetti del Programma ESPON 2013, acronimo di European Observation Network for Territorial Development and Cohesion. I testi sintetizzano ed evidenziano, tra l’altro, le relazioni con le politiche di sviluppo regionale dell’Italia, inserendole in un quadro di cooperazione transnazionale che coinvolge 28 + 4 paesi dell’Unione europea. Affrontando aspetti della politica territoriale europea che spaziano dall’innovazione e conoscenza all’accessibilità, dal policentrismo alle aree metropolitane, dalla migrazione alla globalizzazione, gli Autori mettono in luce la posizione dell’Italia e delle regioni anche rispetto agli obiettivi fissati da Europe 2020. Uno spazio è dedicato alle esperienze regionali che hanno trovato in ESPON uno stimolo e un’occasione di confronto; come pure ai concetti che sottendono il lessico, i principi di orientamento e i nuovi modelli della pianificazione in Europa; e alle esperienze formative rivolte alle giovani generazioni e ai decision maker Il libro si inquadra nelle iniziative del Semestre di Presidenza Italiana dell’Unione europea ed è cofinanziato dal Ministero delle Infrastrutture e dei Trasporti (MIT) responsabile nazionale del Programma ESPON. E’ rivolto ai ricercatori, agli utilizzatori istituzionali, ai policy maker, ai “practioner” e ai “non specialisti”, tra cui gli studenti, affinché possano fare propri i risultati dell’impegno costante, rigoroso e rispettoso delle diversità territoriali che hanno contraddistinto, dal 2007 ad oggi, il contributo della ricerca, anche sperimentale e applicata, alla crescita della società italiana come parte integrante del sistema europeo. L’Osservatorio ESPON, per chi ancora non lo conosce, può rappresentare un viaggio nel territorio europeo, nelle sue diversità territoriali, economiche, sociali, culturali da integrare e rendere coese, sostenibili, mantenendo e sviluppando potenziali di competitività crescenti e, nel contempo, innovando e diffondendo nuovi modi, metodologie, strumenti e prassi per fare del territorio un bene comune e condiviso. Dati, riferimenti e raccomandazioni politiche utili alla crescita del Paese completano il quadro. Presentazione del Ministro delle Infrastrutture, On. Maurizio Lupi Postfazione del Direttore della Coordination Unit del Programma ESPON, Peter MehlbyeThe book is part of the activities of ESPON Contact Point Italy. It includes the results of the contribution of the Italian partners in the development of projects under the ESPON 2013 Programme, which stands for European Observation Network for Territorial Development and Cohesion. The texts summarise and highlight, among other things, the relations with the regional development policies of Italy, placing them in a framework of transnational cooperation involving the 28 + 4 EU Countries. Addressing aspects of European territorial policy, ranging from innovation and knowledge accessibility, from the polycentrism to metropolitan areas, from migration to globalization, the authors highlight the position of Italy and of regions also in relation to the objectives set by Europe 2020. A place is devoted to the regional experiences that in the ESPON found a stimulus and an opportunity for discussion, as well as to the concepts behind the vocabulary, to the principles of guidance, and new planning models in Europe, and to the training experiences aimed at the younger generations and the decision makers The book forms part of the initiatives of the Italian Presidency of the European Union and is co-financed by the Ministry of Infrastructure and Transportation (MIT) in charge of the national ESPON Programme. It is aimed at researchers, institutional users, policy makers, at "practitioners" and "non-specialists" including students, so that they can make use of the results of the constant and rigorous work also respectful of the territorial diversities that have characterized the experimental and applied research since 2007, so contributing to the growth of Italian society as an integral part of the European system. The ESPON Monitoring Centre, for those who still do not know, can be a journey into the European territory, its territorial, economic, social, cultural diversities to integrate and make cohesive and sustainable, by maintaining and developing the increasing potentials of competitiveness and, at the same time, by innovating and disseminating new ways, methodologies, tools and practices to make the territory a common and shared good. Data, references and useful policy recommendations to the growth of the country are also included in the book. Presentation by the Minister of Infrastructure, Mr. Maurizio Lupi Afterword by the Director of the Coordination Unit ESPON Programme , Peter Mehlby

Pathogen reduction/inactivation of products for the treatment of bleeding disorders:what are the processes and what should we say to patients?

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered

Approssimarsi alla povert\ue0 tra teorie, esperienze e buone prassi. Riflessioni di Pedagogia sociale

Un approccio pedagogico al tema della povert\ue0, che rimette al centro la persona povera, i percorsi esistenziali che hanno determinato la situazione di vulnerabilit\ue0 sociale, i bisogni e i desideri dei soggetti, i limiti degli interventi di aiuto politico-sociali e soprattutto le risorse e gli spazi di libert\ue0 su cui \ue8 ancora possibile lavorare per costruire un percorso di emancipazione

Speeding up sustainable solution-phase peptide synthesis using T3P® as a green coupling reagent: methods and challenges

In peptide synthesis, the issues related to poor sustainability, long reaction times and high process mass intensity (PMI) are necessary to promote actions aimed at redefining procedural aspects pro jected towards more sustainable synthetic processes. Herein, we report a fast, widely applicable and green solution-phase peptide synthesis (GSolPPS) via a continuous protocol using propylpho sphonic anhydride T3P® as the coupling reagent and N-benzyloxycarbonyl-protecting group (Z), which is easily removed by hydrogenation. Because N,N-dimethylformamide (DMF) replacement was a priority, the iterative process was per formed in EtOAc, pushing further on overall sustainability. The efficiency of the synthetic protocol in terms of conversion, racemi zation and reaction times allowed extending the scope of the work to the synthesis of the standard peptide Leu-enkephalin as a proof of concept. Among the various explored procedures, the one-pot protocol (Acont plus), avoiding work-ups, intermediate purification and any dispersion effect, allowed the achievement of PMI = 30 for each deprotection/coupling sequence necessary to introduce a single amino acid in the iterative process, without considering the possibility of solvent and base recovery. This value is the lowest reported for an oligopeptide synthesis protocol to dat

Compression estimates for a class of dictionary based compressors

In this paper we consider a parsing algorithm originally introduced in [1] for estimating the information content of symbolic strings generated by various dynamical systems and biological data. Here we show how a suitable coding of the dictionary is sufficient to turn it into an optimal compressor

A similarity measure for biological signals: new applications to HRV analysis

Here we introduce and discuss a recently defined distance function between symbolic strings . Application to phylogenetic tree construction and HRV analysis are considered