Davide Capelli Pagina Personale

Davide Capelli

Tel: +39 06 90672922
E-mail: davide.capelliATic.cnr.it
Address: CNR – Institute of Crystallography
Via Salaria – km 29,300
00015 Monterotondo, Rome ITALY

Current position: Researcher

Curriculum vitae:
2017 to present: Researcher at Institute of Crystallography – CNR
2017: PhD in Biochemistry, University of Rome “La Sapienza”, with thesis “Biostructural studies on PPAR nuclear receptors”
2011 – 2016: Research grant at Institute of Crystallography – CNR
2010: Master’s degree in Pharmaceutical Biotechnology, University of Rome “La Sapienza”
2007: Bachelor’s degree in Biotechnology, University of Rome “Tor Vergata”

Research activity:
Design and X-ray characterization of novel ligands of the nuclear receptors PPARs (Peroxisome Proliferator-Activated Receptors) and inhibitors of Matrix Metalloproteinases (MMPs).
Screening of compound libraries and analysis of protein-ligand interactions through Surface Plasmon Resonance (SPR).

PPARs are transcription factors regulating the lipidic metabolism and the glucose homeostasis. They are target of synthetic ligands for the treatment of type 2 diabetes and obesity. For instance, the thiazolidinedione (TZD) anti-diabetic agents are PPARgamma agonists whose insulin-sensitizing action is well known in the adipose tissues. However, despite their wide prescription PPAR-activating drugs revealed unwanted side effects that cannot be underestimated. For this reasons novel PPARgamma ligands have been identified that are superior therapeutic agents for metabolic disease, such as PPARalpha/gamma dual agonists and PPAR selective modulators (SPPARMs) which present fewer adverse effects. In the last years our group developed novel PPARalpha/gamma dual agonists with improved therapeutic efficacy and reduced side effects. X-ray studies and MD simulations on the complexes between PPARs and these ligands allowed an explanation at molecular level for their different pharmacological profile and allowed to get insight into the mechanism of partial agonism in PPARs. Moreover, we discovered new modes of binding of the ligands that could be exploited for a more fine modulation of the transactivation activity.

Publications:

1.  Peiretti F., Montanari R., Capelli D., Bonardo B., Colson C., Amri E., Grimaldi M., Balaguer P., Ito K., Roeder R.G., Pochetti G., Brunel J.M. “A novel N-substituted valine derivative with unique peroxisome proliferator-activated receptor γ binding properties and biological activities”. J Med Chem 2020 November; 63(21),13124-13139. doi: 10.1021/acs.jmedchem.0c01555
2.  Laghezza A., Piemontese L., Brunetti L., Caradonna A., Agamennone M., Di Pizio A., Pochetti G., Montanari R., Capelli D., Tauro M., Loiodice F. and Tortorella P. “Bone-Seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy”. Pharmaceuticals 2020 May; 13(6),113. doi: 10.3390/ph13060113
3. Montanari R., Capelli D., Yamamoto K., Awaishima H., Nishikata K., Barendregt A., Heck A.J.R., Loiodice F., Alteiri F., Paiardini A., Grottesi A., Pirone L., Pedone E., Peiretti F., Brunel J.M., Itoh T., Pochetti G. “Insights into PPARγ phosphorylation and its inhibition mechanism”. J Med Chem. 2020 May; 63(9):4811-4823. doi: 10.1021/acs.jmedchem.0c00048
4. Capelli D., Parravicini C., Pochetti G., Montanari R., Temporini C., Rabuffetti M., Trincavelli M.L., Daniele S., Fumagalli M., Saporiti S., Bonfanti E., Abbracchio M.P., Eberini I., Ceruti S., Calleri E. and Capaldi S. “Surface Plasmon Resonance as a tool for ligand binding investigation of engineered GPR17 receptor, a G protein coupled receptor involved in myelinization”. Front Chem. 2020 Jan; 7:910. doi: 10.3389/fchem.2019.00910
5. Laghezza A., Piemontese L., Cerchia C., Montanari R., Capelli D., Giudici M., Crestani M., Tortorella P., Peiretti F., Pochetti G., Lavecchia A., Loiodice F. “Identification of the first PPAα/γ able to bind to canonical and alternate sites of PPARγ and to inhibit its Cdk-5-mediated phosphorylation”. J Med Chem. 2018 Sep; doi: 10.1021/acs.jmedchem.8b00835
6. Brusotti G., Montanari M., Capelli D., Cattaneo G., Laghezza A., Tortorella P., Loiodice F., Peiretti F., Bonardo B., Paiardini A., Calleri E. & Pochetti G. ” Betulinic acid is a PPARγ antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis”. Sci Rep. 2017 Jul; 7:5777. doi:10.1038/s41598-017-05666-6
7. Petrosino M., Lori L., Pasquo A., Clorinda Lori, Consalvi V., Minicozzi V., Morante S., Laghezza A., Giorgi A., Capelli
D., and Chiaraluce R. “Single-Nucleotide Polymorphism Protein at the Crossroads of Physiological and Pathological Processes”. Int J Mol Sci. 2017 Feb; 18(2): 361. doi:10.3390/ijms18020361
8. Capelli D., Cerchia C., Montanari R., Loiodice F., Tortorella P., Laghezza A., Pochetti G. and Lavecchia A.. “Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode”. Sci Rep. 2016 Oct; 6:34792. doi:10.1038/srep34792
9. Tauro M., Laghezza A., Loiodice F., Piemontese L., Caradonna A., Capelli D., Montanari R., Pochetti G., Di Pizio A., Agamennone M., Campestre C., Tortorella P. “Catechol-based matrix metalloproteinase inhibitors with additional anti-oxidative activity”. J Enzyme Inhib Med Chem. 2016 Aug; 24:1-13. doi:10.1080/1475366.2016.1217853
10. Montanari R., Capelli D., Tava A., Galli A., Laghezza A., Tortorella P., Loiodice F., Pochetti G. “Screening of saponins and sapogenins from Medicago species as potential PPARγ agonists and X-ray structure of the complex PPARγ/caulophyllogenin”. Sci Rep. 2016 Jun; 6:27658. doi:10.1038/srep27658
11. Laghezza A., Montanari R., Lavecchia A., Piemontese L., Pochetti G., Iacobazzi V., Infantino V., Capelli D., De Bellis M., Liantonio A., Pierno S., Tortorella P., Conte Camerino D., Loiodice F. “On the metabolically active form of metaglidasen: improved synthesis and investigation of its peculiar activity on peroxisome proliferator-activated receptors and skeletal muscles”. ChemMedChem. 2015 Mar; 10(3):555-65. doi:10.1002/cmdc.201402462
11. Lori C., Pasquo A., Montanari R., Capelli D., Consalvi V., Chiaraluce R., Cervoni L., Loiodice F., Laghezza A., Aschi M., Giorgi A., Pochetti G. “Structural basis of the transactivation deficiency of the human PPARγ F360L mutant associated with familial partial lipodystrophy”. Acta Crystallogr D Biol Crystallogr. 2014 Jul; 70(Pt 7):1965-76. doi:10.1107/S1399004714009638
12. Calleri E., Pochetti G., Dossou K.S.S, Laghezza A., Capelli D., Montanari R., , Prada E., Loiodice F., Massolini G., Bernier M and Moaddel R. “Resveratrol and its metabolites bind to PPARs”. Chembiochem. 2014 May; 15(8):1154-60. doi: 10.1002/cbic.201300754
13. Laghezza A., Pochetti G., Lavecchia A., Fracchiolla G., Faliti S., Piemontese L., Di Giovanni C., Iacobazzi V., Infantino V., Montanari R., Capelli D., Tortorella P.,Loiodice F. “New 2-Aryloxy-3-phenil propanoic acids as Peroxisome Proliferator- Activated Receptors aplha/gamma dual agonists able to upregulate the mitochondrial carnitine shuttle system gene expression”. J Med Chem. 2013; 56(1):60-72. doi:10.1021/jm301018z