A Semisynthetic Approach to New Immunoadjuvant Candidates: Site-Selective Chemical Manipulation of Escherichia coli Monophosphoryl Lipid A.
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.
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.
Daniele
D
D'Alonzo
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.|Department of Biology, University "Roma Tre", Viale G. Marconi 446, 00146, Rome, Italy.
Manuela
M
Cipolletti
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.|Cardiff Catalysis Institute, School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT, Cardiff, The United Kingdom.
Giulia
G
Tarantino
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.
Marcello
M
Ziaco
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.
Giuseppina
G
Pieretti
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.
Alfonso
http://orcid.org/0000-0001-7536-6128
A
Iadonisi
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.
Giovanni
http://orcid.org/0000-0003-3757-4967
G
Palumbo
Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138, Naples, Italy.
Alberto
A
Alfano
Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138, Naples, Italy.
Mariateresa
http://orcid.org/0000-0002-7338-9200
M
Giuliano
Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138, Naples, Italy.
Mario
M
De Rosa
Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138, Naples, Italy.
Chiara
http://orcid.org/0000-0002-1066-843X
C
Schiraldi
Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138, Naples, Italy.
Marcella
M
Cammarota
Department of Biology, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy.
Michelangelo
http://orcid.org/0000-0001-8858-3623
M
Parrilli
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy. ebedini@unina.it.
Emiliano
http://orcid.org/0000-0003-4923-3756
E
Bedini
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, 80126, Naples, Italy. corsaro@unina.it.
Maria M
http://orcid.org/0000-0002-6834-8682
MM
Corsaro
D000276:Adjuvants, Immunologic; D004926:Escherichia coli / Q000737:chemistry; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry
D000276:Adjuvants, Immunologic; D008050:Lipid A; C048436:monophosphoryl lipid A
carbohydrates; glycolipids; immunology; lipids; synthetic methods