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Antibody Recognition in multiple sclerosis and rett syndrome using a collection of linear and cyclicN-glucosylated antigenic probes
- Source :
- Biopolymers. 104:560-576
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- Antibody detection in autoimmune disorders, such as multiple sclerosis (MS) and Rett syndrome (RTT) can be achieved more efficiently using synthetic peptides. The previously developed synthetic antigenic probe CSF114(Glc), a type I' beta-turn N-glucosylated peptide structure, is able to recognize antibodies in MS and RTT patients' sera as a sign of immune system derangement. We report herein the design, synthesis, conformational analysis, and immunological evaluation of a collection of glycopeptide analogs of CSF114(Glc) to characterize the specific role of secondary structures in MS and RTT anti-body recognition. Therefore, we synthesized a series of linear and cyclic short glucosylated sequences, mimicking different b-turn conformations, which were evaluated in inhibition enzyme-linked immunosorbent assays (ELISA). Calculated IC50 ranking analysis allowed the selection of the candidate octapeptide containing two (S) 22-amino-4-pentynoic acid (L-Pra) residues Ac-PraRRN(Glc) GHT-Pra-NH2, with an IC50 in the nanomolar range. This peptide was adequately modified for solidphase ELISA (SP-ELISA) and surface plasmon resonance (SPR) experiments. Pra-RRN(Glc) GHT-Pra-NH2 peptide was modified with an alkyl chain linked to the N-terminus, favoring immobilization on solid phase in SP-ELISA and differentiating IgG antibody recognition between patients and healthy blood donors with a high specificity. However, this peptide displayed a loss in IgM specificity and sensitivity. Moreover, an analog was obtained after modification of the octapeptide candidate Ac-Pra-RRN(Glc) GHT-Pra-NH2 to favor immobilization on SPR sensor chips. SPR technology allowed us to determine its affinity (K-D=16.4 nM), 2.3 times lower than the affinity of the original glucopeptide CSF114(Glc) (K-D=7.1 nM).
- Subjects :
- chemistry.chemical_classification
0303 health sciences
biology
010405 organic chemistry
Chemistry
Glycoconjugate
Organic Chemistry
Biophysics
Peptide
General Medicine
01 natural sciences
Biochemistry
Glycopeptide
3. Good health
0104 chemical sciences
Biomaterials
03 medical and health sciences
Protein structure
Antigen
biology.protein
Surface plasmon resonance
Antibody
IC50
030304 developmental biology
Subjects
Details
- ISSN :
- 00063525
- Volume :
- 104
- Database :
- OpenAIRE
- Journal :
- Biopolymers
- Accession number :
- edsair.doi...........b9b0d383de0b755216174bda1ed389c6