130,294 research outputs found
SALICYLALDEHYDE-TAGGED PEPTIDES FOR THE REVERSIBLE-COVALENT ENGAGEMENT OF PROTEIN LYSINE RESIDUES
No full textInserting electrophilic species into small molecule ligands or peptides is a well-established method for enhancing binding affinity to target proteins. The amino acid Lysine (Lys) is highly abundant in the proteome and one of the most frequent residues on the outer structural layers of proteins. For these reasons, the derivatization of synthetic ligands with aldehyde tags capable of imine bond formation with Lys ɛ-amino groups may represent a general strategy for the discovery of potent small-molecule inhibitors.
Ortho-hydroxy aldehydes such as pyridoxal or salicylaldehyde (SA) derivatives have been used to form imines in aqueous media, stabilized by an intramolecular H-bond between the imine N atom and the ortho-phenolic proton. By virtue of this reactivity, SA derivatives are being installed into various classes of protein ligands, aimed at the reversible-covalent engagement of protein Lys residues.1,2
This talk will describe our recent contribution to this field, with focus on the installation of the Lys-engaging SA module into peptide ligands.3,4
Figure 1. Left: Binding mechanism of a reversible-covalent ligand equipped with a salicylaldehyde (SA) tag. Ideally, SA forms a remarkably stable imine bond with a Lys(ε-NH2) residue proximal to the ligand binding site. This covalent ligand-protein connection is stabilized by a H bond between the OH phenolic proton and the imine N atom. As a result, the final ligand-protein complex is stabilized by a combination of non-covalent and covalent interactions. Right: Current options for the SA tag installation at different peptide positions, recently developed by our group.
References
1. A. Dal Corso, M. Catalano, A. Schmid, J. Scheuermann, D. Neri, Angew. Chem. Int. Ed. 2018, 57, 17178.
2. M. Mason, L. Belvisi, L. Pignataro, A. Dal Corso, ChemBioChem 2023, e202300743.
3. G. Sacco, D. Arosio, M. Paolillo, A. Gloger, J. Scheuermann, L. Pignataro, L. Belvisi, A. Dal Corso, C. Gennari, Chem. Eur. J. 2023, e202203768.
4. M. Mason, B. Nava, L. Belvisi, L. Pignataro, A. Dal Corso, Eur. J. Org. Chem. 2024, 27, 202400229
Positive Organization Questionnaire and Appreciative Inquiry: adopting a strengths-based approach to promote organizational well-being and performance
No full textThis contribution aims to emphasize the benefits offered by the approach based on the research perspective-intervention and in line with the “appreciative research”, which deals with the strengths of individuals, groups and organizations, as defined by Cooperrider and Whitney (2005). The Positive Organization Questionnaire (POQ) (NA De Carlo, L. Dal Corso, & A. De Carlo, 2015) moves in fact from the consideration of the importance of adopting a strenghts-based approach and has been built to be used as a tool of detection and activation of the awareness processes and responsibilities of supervisors and workers, in reference to their task and relations with colleagues and collaborators. This tool, then, is in line with the approach of the Appreciative Inquiry (AI) that has similar objectives. On this basis a research-action intervention was developed by focusing on a services company to highlight the desired future (dream) even in the face of evolving challenging faced by both the people and their organization. The results show the positive effects of the interventions based on POQ and their greater overall effectiveness through integration with the AI approach
L'Athenaion Politeia (P. Lond. Lit. 108) e la sua 'biblioteca': libri e mani nella chora egizia
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Anthony Grafton - Megan Williams, Come il cristianesimo ha trasformato il libro. Edizione italiana a cura di Lucio Del Corso e Laura Lulli
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In vitro plant regeneration of the heavy metal tolerant and hyperaccumulator Arabidopsis halleri (Brassicaceae)
No full textPlants were regenerated from root explants of Arabidopsis halleri (L.) O'Kane and Al-Shehbaz via a three-step procedure callus induction, induction of somatic embryos and shoot development. Callus was induced from root segments, leaflets and petiole segments after incubation for 2 weeks in Murashige and Skoog medium (MS) supplemented with 0.5 mg/l -1 (2.26 μM) 2,4-D (2,4-dichlorophenoxyacetic acid) and 0.05 mg/l -1 (0.23 μM) kinetin. Only calli developed from root segments continued to grow when transferred to a regeneration medium containing 2.0 mg/l -1 (9.8 μM) 6-γ-γ-(dimethylallylamino)-purine (2ip) and 0.05 mg/l -1 (2.68 μM) α-naphthalenacetic acid (NAA) and eventually 40 of them developed embryogenic structures. On the same medium 38 of these calli regenerated shoots. Rooting was achieved for 50 of the shoots subcultured in MS medium without hormones. The regeneration ability of callus derived from root cuttings, observed in this study, makes this technique useful for genetic transformation experiments and in vitro culture studie
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