PMID- 30518150
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2076-3425 (Print)
IS  - 2076-3425 (Electronic)
IS  - 2076-3425 (Linking)
VI  - 8
IP  - 12
DP  - 2018 Dec 4
TI  - Design of Linear and Cyclic Mutant Analogues of Dirucotide Peptide (MBP(82(-)98)) 
      against Multiple Sclerosis: Conformational and Binding Studies to MHC Class II.
LID - 10.3390/brainsci8120213 [doi]
LID - 213
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disorder of the central 
      nervous system. MS is a T cell-mediated disease characterized by the 
      proliferation, infiltration, and attack of the myelin sheath by immune cells. 
      Previous studies have shown that cyclization provides molecules with strict 
      conformation that could modulate the immune system. METHODS: In this study, we 
      synthesized peptide analogues derived from the myelin basic protein (MBP)(82(-)98) 
      encephalitogenic sequence (dirucotide), the linear altered peptide ligand 
      MBP(82(-)98) (Ala(91)), and their cyclic counterparts. RESULTS: The synthesized 
      peptides were evaluated for their binding to human leukocyte antigen (HLA)-DR2 
      and HLA-DR4 alleles, with cyclic MBP(82(-)98) being a strong binder with the 
      HLA-DR2 allele and having lower affinity binding to the HLA-DR4 allele. In a 
      further step, conformational analyses were performed using NMR spectroscopy in 
      solution to describe the conformational space occupied by the functional amino 
      acids of both linear and cyclic peptide analogues. This structural data, in 
      combination with crystallographic data, were used to study the molecular basis of 
      their interaction with HLA-DR2 and HLA-DR4 alleles. CONCLUSION: The cyclic and 
      APL analogues of dirucotide are promising leads that should be further evaluated 
      for their ability to alter T cell responses for therapeutic benefit against MS.
FAU - Deraos, George
AU  - Deraos G
AD  - Department of Chemistry, University of Patras, 26500 Patras, Greece. 
      deraos@gmail.com.
AD  - ELDrug S.A., Patras Science Park, Platani, 26504 Patras, Greece. 
      deraos@gmail.com.
FAU - Kritsi, Eftichia
AU  - Kritsi E
AD  - Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic 
      Research Foundation, 11635 Athens, Greece. ekritsi@eie.gr.
FAU - Matsoukas, Minos-Timotheos
AU  - Matsoukas MT
AUID- ORCID: 0000-0002-4642-8163
AD  - Department of Pharmacy, University of Patras, 26500 Patras, Greece. 
      minmatsoukas@gmail.com.
FAU - Christopoulou, Konstantina
AU  - Christopoulou K
AD  - Department of Chemistry, University of Patras, 26500 Patras, Greece. 
      christopouloucon@gmail.com.
AD  - ELDrug S.A., Patras Science Park, Platani, 26504 Patras, Greece. 
      christopouloucon@gmail.com.
FAU - Kalbacher, Hubert
AU  - Kalbacher H
AD  - Interfaculty Institute of Biochemistry, University of Tubingen, 72076 Tubingen, 
      Germany. kalbacher@uni-tuebingen.de.
FAU - Zoumpoulakis, Panagiotis
AU  - Zoumpoulakis P
AUID- ORCID: 0000-0001-9348-6078
AD  - Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic 
      Research Foundation, 11635 Athens, Greece. pzoump@eie.gr.
FAU - Apostolopoulos, Vasso
AU  - Apostolopoulos V
AUID- ORCID: 0000-0001-6788-2771
AD  - Institute for Health and Sport, Victoria University, Melbourne VIC 3030, 
      Australia. vasso.apostolopoulos@vu.edu.au.
FAU - Matsoukas, John
AU  - Matsoukas J
AD  - Department of Chemistry, University of Patras, 26500 Patras, Greece. 
      imats1953@gmail.com.
AD  - ELDrug S.A., Patras Science Park, Platani, 26504 Patras, Greece. 
      imats1953@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20181204
PL  - Switzerland
TA  - Brain Sci
JT  - Brain sciences
JID - 101598646
PMC - PMC6316436
OTO - NOTNLM
OT  - HLA-DR2
OT  - HLA-DR4
OT  - MBP
OT  - MS
OT  - altered peptide ligand
OT  - cyclic peptide
OT  - dirucotide
OT  - multiple sclerosis
OT  - myelin basic protein
COIS- The authors declare no conflict of interest.
EDAT- 2018/12/07 06:00
MHDA- 2018/12/07 06:01
PMCR- 2018/12/01
CRDT- 2018/12/07 06:00
PHST- 2018/11/20 00:00 [received]
PHST- 2018/11/30 00:00 [accepted]
PHST- 2018/12/07 06:00 [entrez]
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2018/12/07 06:01 [medline]
PHST- 2018/12/01 00:00 [pmc-release]
AID - brainsci8120213 [pii]
AID - brainsci-08-00213 [pii]
AID - 10.3390/brainsci8120213 [doi]
PST - epublish
SO  - Brain Sci. 2018 Dec 4;8(12):213. doi: 10.3390/brainsci8120213.