A Semisynthetic Approach to New Immunoadjuvant Candidates: Site-Selective Chemical Manipulation of Escherichia coli Monophosphoryl Lipid A.
Daniele D'AlonzoManuela CipollettiGiulia TarantinoMarcello ZiacoGiuseppina PierettiAlfonso IadonisiGiovanni PalumboAlberto AlfanoMariateresa GiulianoMario De RosaChiara SchiraldiMarcella CammarotaMichelangelo ParrilliEmiliano BediniMaria Michela CorsaroPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2016)
A semisynthetic approach to novel lipid A derivatives from Escherichia coli (E. coli) lipid A is reported. This methodology stands as an alternative to common approaches based exclusively on either total synthesis or extraction from bacterial sources. It relies upon the purification of the lipid A fraction from fed-batch fermentation of E. coli, followed by its structural modification through tailored, site-selective chemical reactions. In particular, modification of the lipid pattern and functionalization of the phosphate group as well as of the sole primary hydroxyl group were accomplished, highlighting the unusual reactivity of the molecule. Preliminary investigations of the immunostimulating activity of the new semisynthetic lipid A derivatives show that some of them stand out as promising, new immunoadjuvant candidates.