title: Mannosylated Linear and Cyclic Single Amino Acid Mutant Peptides Using a Small 10 Amino Acid Linker Constitute Promising Candidates Against Multiple Sclerosis.
abstract: Multiple sclerosis (MS) is a serious autoimmune demyelinating disease leading to loss of neurological function. The design and synthesis of various altered peptide ligands of immunodominant epitopes of myelin proteins to alter the autoimmune response, is a promising therapeutic approach for MS. In this study, linear and cyclic peptide analogs based on the myelin basic protein 83-99 (MBP83-99) immunodominant epitope conjugated to reduced mannan via the (KG)5 and keyhole limpet hemocyanin (KLH) bridge, respectively, were evaluated for their biological/immunological profiles in SJL/J mice. Of all the peptide analogs tested, linear MBP83-99(F(91)) and linear MBP83-99(Y(91)) conjugated to reduced mannan via a (KG)5 linker and cyclic MBP83-99(F(91)) conjugated to reduce mannan via KLH linker, yielded the best immunological profile and constitute novel candidates for further immunotherapeutic studies against MS in animal models and in human clinical trials.
authors.affiliation: Immunology and Vaccine Laboratory, Burnet Institute , Melbourne, VIC , Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Day
authors.affiliation: Department of Chemistry, University of Patras , Patras , Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Tselios
authors.affiliation: Department of Chemistry, University of Patras , Patras , Greece ; Eldrug S.A. , Patras , Greece.
authors.forename: Maria-Eleni
authors.initials: ME
authors.lastname: Androutsou
authors.affiliation: Department of Chemistry, University of Patras , Patras , Greece.
authors.forename: Anthi
authors.initials: A
authors.lastname: Tapeinou
authors.affiliation: Department of Chemistry, University of Patras , Patras , Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Frilligou
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University , Melbourne, VIC , Australia.
authors.forename: Lily
authors.initials: L
authors.lastname: Stojanovska
authors.affiliation: Department of Chemistry, University of Patras , Patras , Greece ; Eldrug S.A. , Patras , Greece.
authors.forename: John
authors.initials: J
authors.lastname: Matsoukas
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University , Melbourne, VIC , Australia.
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
keywords: MBP83–99; altered peptide ligands; mannan; multiple sclerosis; myelin basic protein