M Saviano 23oct2023

CAPT Seminar - DR Michele SavianoLundi, 11h00 - Amphi IPREM

Le 23 oct. 2023 à 11h00

Dr Michele Saviano

(Research Directeur at the Institute of Crystallography , CNR Italy)

Lundi 23 octobre, 11h - Amphi IPREM

"Toward Personalized Medicine: RGD-Peptide as Scaffold for the Comprehension of Structural Determinants for Integrin Specific Recognition"

Abstract:
Since integrins are involved in the regulation of physiological processes, as well as in pathological ones, the development of integrin subtype-selective antagonists is highly desirable. Integrins avb3 and a5b1, key mediators of cell adhesion, differentiation, proliferation, angiogenesis and tumor growth, have been considered very promising targets for theranostic application. Due to the similarity of the RGD binding regions in these integrins, the development of small synthetic molecules with high activity and selectivity for the different subtypes is a tricky goal to pursue. In the last decade, we designed and
characterized the chimeric molecule RGDechi, a peptide selective for avb 3 [1]. We demonstrated anti-adhesive and proapoptotic effects on tumor cells and antiangiogenic activity in vivo [2-4]. In addition, SPECT and PET imaging studies with 111In and 18Flabelled RGDechi in a xenograft model confirmed the ability of peptide to selectively visualize this integrin. Recently, NMR and computational analyses on cell membranes allowed a detailed understanding of avb3/RGDechi recognition mechanism [5]. Herein we have investigated the capability of the peptide to bind a5b1 integrin and characterized the molecular determinants governing this interaction through a combined experimental and computational approach.

The detailed comparison of RGDechi/a5b1 structural model with that, previously, determined of RGDechi in complex with avb3 has shown how the chimeric nature of the peptide renders the molecule an important scaffold to recognize integrins with different recognition modalities, providing insight on the structural requirements needed to design novel peptides selective for a5b1 to use in theranostics [6-7].

References
[1] Del Gatto, A. et al. J Med Chem., 2006, 49, 3416-3420
[2] Zannetti, A. et al. Clin Cancer Res., 2009 15, 5224-5233
[3] Santulli, G. et al. J Transl Med., 2011, 9, 7
[4] Pisano, M. et al. Anticancer Res., 2013, 33, 871-879.
[5] Farina B, et al. Chemistry, 2016, 22, 681-693.
[6] Farina B, et al. J Pept Sci, 2019. Mar 18:e3166
[7] Acconcia C, et al. Int J Mol Sci., 2022, 23(19):11039.

CURRICULUM VITAE of Michele Saviano

Michele Saviano born in Naples, Italy on September 21, 1964 and received his PhD in Industrial Chemistry at University of Naples, Faculty of Science, in March 1988. From 1989 to 1992, he was CNR Researcher at the Centro di Studio di Biocristallografia (CNR), Naples. From 1992 to 1998, he was Associated Researcher of Inorganic and General Chemistry at Faculty of Science of University of Naples “Federico II”. From 1998 to 2006, he was Senior Researcher at Istituto di Biostrutture e Biommagini (CNR) Naples. From 2007 to 2010, he was Director of Researcher at Istituto di Biostrutture e Biommagini (CNR) Naples. From 2010 to 2021, he was Director of the Institute of Crystallography, and from 2021 to this date he is Research Director at the same Institute. During his career he has carried out research activities in various foreign laboratories. He was Visiting Scientist at IBM Corporation "Scientific Engineering Computations Data Systems Division" in Kingston as Visiting Researcher, New York, USA, developing molecular dynamics techniques on peptide systems; Visiting Scientist at the Gustaf H. Carlson School of Chemistry, Clark University, Worchester, Massachusetts, USA, developing computational procedures such as MD and "Distance Geometry" to analyze peptide systems; Professeur de Chimie at Faculty of Science of the Université Henri Poincaré, Nancy 1, Vandoeuvres-lès-Nancy Cedex, France.In 1998 he has been the recipient of the "AIC Award" by the Italian Association of Crystallography in recognition of his outstanding contribution to the analysis with crystallographic and computational techniques of bioactive systems.
His research interests lie in chemistry of bioactive systems: the relationships between structure and activity of numerous bioactive systems have been the object of his investigations, carried out with a variety of experimental and theoretical techniques, for the understanding of the mechanism of action of biologically relevant systems. In particular, his studies include: a) de novo protein, oligonucleotides and peptide design; b) rational design of conformationally constrained analogs of bioactive peptides with enhanced in vivo selectivity, affinity, and stability; c) development of computational procedures in the conformational analysis of bioactive molecules at different complexity; d) analysis with different computational techniques of modified oligonucleotides and their interaction with proteins or with DNA and RNA; d) chemistry and conformational properties of peptides containing non natural amino acid residues; e) study of the preferred conformations in solution (by NMR, FT-IR, CD) and in the crystal state (by X-ray diffraction) of bioactive molecular systems.
He is author of about 240 full paper published on international journals, 3 patents, and many lectures to national and international congresses. He has also established many collaborations with a great number of scientists, involved in chemistry of bioactive systems, all over the world. Furthermore he has many ongoing links with industries, both large internationally established firms and small and medium size Italian enterprises.
Scopus- H-index: 35; Google Scholar- H-index: 38