Recently, we described synthetic sulfolipids named Sulfavants as a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. The members of this family, Sulfavant A (), Sulfavant R (), and Sulfavant S (), showed important effects on triggering receptor expressed on myeloid cells 2 (TREM2)-induced differentiation and maturation of human dendritic cells (hDC), through a novel cell mechanism underlying the regulation of the immune response. As these molecules are involved in biological TREM2-mediated processes crucial for cell survival, here, we report the synthesis and application of a fluorescent analogue of Sulfavant A bearing the 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza--indacene moiety (Me-BODIPY). The fluorescent derivative, named PB-SULF A (), preserving the biological activity of Sulfavants, opens the way to chemical biology and cell biology experiments to better understand the interactions with cellular and organ targets and to improve our comprehension of complex molecular mechanisms underlying the not fully understood ligand-induced TREM2 activity.
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http://dx.doi.org/10.1021/acs.analchem.3c04322 | DOI Listing |
Anal Chem
February 2024
Institute of Biomolecular Chemistry (CNR), Via Campi Flegrei 34, 80078 Pozzuoli, Napoli , Italy.
Recently, we described synthetic sulfolipids named Sulfavants as a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. The members of this family, Sulfavant A (), Sulfavant R (), and Sulfavant S (), showed important effects on triggering receptor expressed on myeloid cells 2 (TREM2)-induced differentiation and maturation of human dendritic cells (hDC), through a novel cell mechanism underlying the regulation of the immune response. As these molecules are involved in biological TREM2-mediated processes crucial for cell survival, here, we report the synthesis and application of a fluorescent analogue of Sulfavant A bearing the 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza--indacene moiety (Me-BODIPY).
View Article and Find Full Text PDFFront Immunol
March 2023
Bio-Organic Chemistry Unit, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
Introduction: Sulfavant A (SULF A) is a synthetic derivative of naturally occurring sulfolipids. The molecule triggers TREM2-related maturation of dendritic cells (DCs) and has shown promising adjuvant activity in a cancer vaccine model.
Methods: the immunomodulatory activity of SULF A is tested in an allogeneic mixed lymphocyte reaction (MLR) assay based on monocyte-derived dendritic cells and naïve T lymphocytes from human donors.
Cell Mol Life Sci
June 2022
Bio-Organic Chemistry Unit, Institute of Bio-Molecular Chemistry, National Research Council, Via Campi Flegrei 34, 80078, Pozzuoli, Italy.
Objective: The immune response arises from a fine balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanism of action of SULF A and addressed the identification of its molecular target in human dendritic cells (hDCs).
View Article and Find Full Text PDFJ Colloid Interface Sci
April 2022
Bio-Organic Chemistry Unit, CNR-Institute of Biomolecular Chemistry, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy. Electronic address:
Sulfavant A and Sulfavant R, sulfoquinovoside-glycerol lipids under study as vaccine adjuvants, structurally differ only for the configuration of glyceridic carbon, R/S and R respectively. The in vitro activity of these substances follows a bell-shaped dose-response curve, but Sulfavant A gave the best response around 20 µM, while Sulfavant R at 10 nM. Characterization of aqueous self-assembly of these molecules by a multi-technique approach clarified the divergent and controversial biological outcome.
View Article and Find Full Text PDFMar Drugs
August 2020
Bio-Organic Chemistry Unit, CNR-Institute of Biomolecular Chemistry, Via Campi Flegrei 34, 80078 Pozzuoli, Italy.
In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton.
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