title: Design, automated synthesis and immunological evaluation of NOD2-ligand-antigen conjugates.
abstract: The covalent attachment of an innate immune system stimulating agent to an antigen can provide active vaccine modalities capable of eliciting a potent immune response against the incorporated antigen. Here we describe the design, automated synthesis and immunological evaluation of a set of four muramyl dipeptide-peptide antigen conjugates. Muramyl dipeptide (MDP) represents a well-known ligand for the intracellular NOD2 receptor and our study shows that covalently linking an MDP-moiety to an antigenic peptide can lead to a construct that is capable of stimulating the NOD2 receptor if the ligand is attached at the anomeric center of the muramic acid. The constructs can be processed by dendritic cells (DCs) and the conjugation does not adversely affect the presentation of the incorporated SIINFEKL epitope on MHC-I molecules. However, stimulation of the NOD2 receptor in DCs was not sufficient to provide a strong immunostimulatory signal.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Marian M J H P
authors.initials: MM
authors.lastname: Willems
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, P. O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Gijs G
authors.initials: GG
authors.lastname: Zom
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Meeuwenoord
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, P. O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Ferry A
authors.initials: FA
authors.lastname: Ossendorp
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Jeroen D C
authors.initials: JD
authors.lastname: Codée
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Filippov
keywords: NOD2 receptor; automated synthesis; glycopeptide; innate immunity; muramyl dipeptide; solid phase synthesis