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Your search keyword '"Malgieri G."' showing total 3 results
Start Over Author "Malgieri G." Journal acs chemical biology
3 results on '"Malgieri G."'

1. Screening a Molecular Fragment Library to Modulate the PED/PEA15-Phospholipase D1 Interaction in Cellular Lysate Environments

Author

Carla Isernia, Emilia Pedone, Marica Sassano, Luigi Russo, Annarita Del Gatto, Gianluca D'Abrosca, Sonia Di Gaetano, Maria Della Valle, Laura Zaccaro, Gaetano Malgieri, Biancamaria Farina, Luciano Pirone, Roberto Fattorusso, Farina, B., Pirone, L., D'Abrosca, G., Della Valle, M., Russo, L., Isernia, C., Sassano, M., Del Gatto, A., Di Gaetano, S., Zaccaro, L., Malgieri, G., Pedone, E. M., and Fattorusso, R.

Subjects
Lysis, Protein Conformation, Ligands, Biochemistry, Organic molecules, Small Molecule Libraries, Type ii diabetes, Phospholipase D, Humans, Nuclear Magnetic Resonance, Biomolecular, Binding Sites, Chemistry, Ligand, Glucose transporter, Insulin sensitivity, Biological Transport, General Medicine, Peptide Fragments, Molecular Docking Simulation, Glucose, Cellular Microenvironment, Diabetes Mellitus, Type 2, Astrocytes, Phosphoprotein, Thermodynamics, Molecular Medicine, Insulin Resistance, Apoptosis Regulatory Proteins, Phospholipase D1, Protein Binding
Abstract

The overexpression of PED/PEA15, the phosphoprotein enriched in diabetes/phosphoprotein enriched in the astrocytes 15 protein (here referred simply to as PED), observed in some forms of type II diabetes, reduces the transport of insulin-stimulated glucose by binding to the phospholipase D1 (PLD1). The inhibition of the PED/PLD1 interaction was shown to restore basal glucose transport, indicating PED as a pharmacological target for the development of drugs capable of improving insulin sensitivity and glucose tolerance. We here report the identification and selection of PED ligands by means of NMR screening of a library of small organic molecules, NMR characterization of the PED/PLD1 interaction in lysates of cells expressing PLD1, and modulation of such interactions using BPH03, the best selected ligand. Overall, we complement the available literature data by providing detailed information on the structural determinants of the PED/PLD1 interaction in a cellular lysate environment and indicate BPH03 as a precious scaffold for the development of novel compounds that are able to modulate such interactions with possible therapeutic applications in type II diabetes.

Published
2021
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2. Screening a Molecular Fragment Library to Modulate the PED/PEA15-Phospholipase D1 Interaction in Cellular Lysate Environments.

Author

Farina B, Pirone L, D'Abrosca G, Della Valle M, Russo L, Isernia C, Sassano M, Del Gatto A, Di Gaetano S, Zaccaro L, Malgieri G, Pedone EM, and Fattorusso R

Subjects
Binding Sites, Biological Transport, Cellular Microenvironment, Glucose, Humans, Insulin Resistance, Ligands, Molecular Docking Simulation, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Conformation, Thermodynamics, Apoptosis Regulatory Proteins chemistry, Astrocytes chemistry, Diabetes Mellitus, Type 2 metabolism, Peptide Fragments chemistry, Phospholipase D chemistry, Small Molecule Libraries chemistry
Abstract

The overexpression of PED/PEA15, the phosphoprotein enriched in diabetes/phosphoprotein enriched in the astrocytes 15 protein (here referred simply to as PED), observed in some forms of type II diabetes, reduces the transport of insulin-stimulated glucose by binding to the phospholipase D1 (PLD1). The inhibition of the PED/PLD1 interaction was shown to restore basal glucose transport, indicating PED as a pharmacological target for the development of drugs capable of improving insulin sensitivity and glucose tolerance. We here report the identification and selection of PED ligands by means of NMR screening of a library of small organic molecules, NMR characterization of the PED/PLD1 interaction in lysates of cells expressing PLD1, and modulation of such interactions using BPH03, the best selected ligand. Overall, we complement the available literature data by providing detailed information on the structural determinants of the PED/PLD1 interaction in a cellular lysate environment and indicate BPH03 as a precious scaffold for the development of novel compounds that are able to modulate such interactions with possible therapeutic applications in type II diabetes.

Published
2021
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3. Structural basis of a temporin 1b analogue antimicrobial activity against Gram negative bacteria determined by CD and NMR techniques in cellular environment.

Author

Malgieri G, Avitabile C, Palmieri M, D'Andrea LD, Isernia C, Romanelli A, and Fattorusso R

Subjects
Antimicrobial Cationic Peptides metabolism, Antimicrobial Cationic Peptides pharmacology, Cell Membrane chemistry, Cell Membrane metabolism, Circular Dichroism, Drug Design, Escherichia coli chemistry, Escherichia coli metabolism, Gram-Negative Bacteria drug effects, Magnetic Resonance Spectroscopy, Protein Conformation, Protein Structure, Tertiary, Proteins pharmacology, Antimicrobial Cationic Peptides chemistry, Proteins chemistry
Abstract

We here report an original approach to elucidate mechanisms of action of antimicrobial peptides and derive crucial structural requirements for the design of novel therapeutic agents. The high resolution structure of TB_KKG6A, an antimicrobial peptide designed to amplify the spectrum of action of Temporin B, bound to E. coli is here determined by means of CD and NMR methodologies. We have also defined, through STD analysis, the residues in closer proximity to the bacterial membrane.

Published
2015
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