Bodipy-Based Fluorescent Analog of the Molecular Vaccine Adjuvants Sulfavants

Session: 
PS2 Poster session 2 Even numbers
Code: 
P60
Location (hall): 
Foyer
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15
Laura
Fioretto

Laura Fioretto1,2, Emiliano Manzo2, Carmela Gallo2, Marcello Ziaco3, Genoveffa Nuzzo2, Marina Della Greca1, Luigi Paduano1, Raffaele De Palma4, Angelo Fontana1

1University of Naples Federico II, Dept of Chemical Sciences, Naples, Italy, 2Bio-Organic Chemistry Unit, CNR-Istituto di Chimica Biomolecolare, Naples, Italy, 3BioSEARCH c/o R&D Site Istituto di Chimica Biomolecolare-CNR, Naples, Italy, 4Second University of Naples- Dept of Precision Medicine, c/o II Policlinico, Naples, Italy

Recently, we described synthetic sulfolipids named Sulfavants (1-3) as a novel class of molecular vaccine adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton.[1,2] These compounds induce maturation of human DCs by the up-regulation of phenotypic markers.[1,3] In particular, Sulfavant A (1), the prototype of this class of molecules, was proved to boost immune protection and to act as an adjuvant in mice in an experimental model of cancer vaccine against a murine B16F10 melanoma cell line, that is widely used for therapeutic evaluation. 

Therefore, the Sulfavants are ideal candidates to be used as vaccine adjuvants in relation to their efficiency properties accompanied by a low possibility of giving side effects.[1] Crucial steps for the pharmacological development of this class of adjuvants are certainly the elucidation of the biological mechanisms, the interactions between these compounds and their cellular targets, the monitoring of their metabolism and the mapping bio-distribution in cells and in vivo. With these purposes, the preparation of fluorescent analogs of Sulfavants is an essential factor for future biological studies. In this regard, we planned a chemical strategy for the synthesis of a Sulfavant fluorescent analog linked to the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene moiety (BODIPY) named Sulfavant R-BODIPY (4). 

The preparation of the Sulfavant R-BODIPY (4) dye was achieved by a versatile diastereoselective synthesis based on the trichloroacetimidate method which opens a straightforward access to a wide class of fluorescent sulfolipids derivatives, essential tools for achieving a better comprehension of the biological mechanisms at the base of adjuvant activity of this class of molecules.

Acknowlegements

Authors thank European Union “PON Ricerca e Innovazione 2014-2020” for funding a Ph.D

References: 
  1. E. Manzo, A. Cutignano, D. Pagano, C. Gallo, G. Barra, G. Nuzzo, C. Sansone, A. Ianora, K. Urbanek, D. Fenoglio, F. Ferrara, C. Bernardi, A. Parodi, G. Pasquale, A. Leonardi, G. Filaci, R. De Palma, A. Fontana, Sci. Rep. 2017, 7, 6286.
  2. E. Manzo, L. Fioretto, D. Pagano, G. Nuzzo, C. Gallo, R. De Palma, A. Fontana, Mar. Drugs, 2017, 15, 288.
  3. E. Manzo, C. Gallo, L. Fioretto, G. Nuzzo, G. Barra, D. Pagano, I. Russo Krauss, L. Paduano, M. Ziaco, M. Della Greca, R. De Palma, and A. Fontana, ACS Omega 2019, 4, 7807-7814.

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