Synthesis of the major encephalitogenic determinant of myelin basic protein and the 13C N.M.R. of some protected intermediates

1977 ◽  
Vol 30 (11) ◽  
pp. 2533 ◽  
Author(s):  
SJ Pasaribu
Keyword(s):  
Myelin Basic Protein ◽  
Catalytic Hydrogenation ◽  
Basic Protein ◽  
Side Chain ◽  
Benzyl Ether ◽  
Protecting Group ◽  
Fragment Condensation

The main encephalitogenic determinant of bovine myelin basic protein (MBP 114-122) has been synthesized through fragment condensation of tetrapeptide, Boc-Phe-Ser-Trp-Gly-OH, and penta-peptide, H-Ala- Glu(OBzl)-Gly-Gln-Lys(Nε-Cbz)-Obzl. It was observed that the benzyl ether protecting group of the serine side chain was not removed during catalytic hydrogenation (Pd/C-H2) of the tetrapeptide, Boc-Phe- Ser(OBzl)-Trp-Gly-OBzl. 13C N.M.R. spectra of some other intermediates are discussed.

Encephalitogenic Peptides: Synthesis and 13C N.M.R. of a Pentapeptide Fragment of Myelin Basic Protein of the (65-74) Region

1979 ◽  
Vol 32 (7) ◽  
pp. 1575 ◽  
Author(s):  
SJ Pasaribu
Keyword(s):  
Myelin Basic Protein ◽  
Conventional Method ◽  
Basic Protein ◽  
Side Chain ◽  
Benzyl Ether ◽  
Protecting Group ◽  
Lower Field ◽  
Trans Conformation ◽  
Upfield Shift ◽  
Peptides Synthesis

The synthesis, by stepwise conventional method, of a fully protected pentapeptide, Boc-Ser(OBzl)- Leu-Pro-Gln-Lys(N8-Cbz)-OBzl, a fragment of the MBP 65-74 region, is described. 13C N.M.R. of the intermediates are discussed, and it was observed that proline gave rise only to the trans- conformation. The benzyl ether protecting group of the serine side chain was found to cause the β-carbon to resonate at a lower field, whereas the α-carbon experienced an upfield shift.

N.M.R. studies on myelin basic protein. I. 13C spectra in aqueous solutions

1978 ◽  
Vol 31 (11) ◽  
pp. 2367 ◽  
Author(s):  
BE Chapman ◽  
WJ Moore
Keyword(s):  
Myelin Basic Protein ◽  
Basic Protein ◽  
Polypeptide Chain ◽  
Random Coil ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Native Protein ◽  
Denatured Protein ◽  
Coil Structure ◽  
Random Coil Structure

Carbon-13 n.m.r, spectra have been obtained for bovine myelin basic protein at pD 4.4 in D2O and in 6 M guanidine deuterochloride solutions. Chemical-shift differences between resonances from some amino acid residues are interpreted in terms of structured regions in the polypeptide chain of the native protein, whereas the denatured protein displays the spectrum expected for an essentially random coil. Measurements of T1 and n.O.e. provide quantitative data on the dynamics of the backbone and side-chain carbons, and give support to the conclusion that the native protein does not have a random-coil structure.

scholarly journals Crystal Structure of HLA-DR2 (DRA*0101, DRB1*1501) Complexed with a Peptide from Human Myelin Basic Protein

1998 ◽  
Vol 188 (8) ◽  
pp. 1511-1520 ◽  
Author(s):  
Kathrine J. Smith ◽  
Jason Pyrdol ◽  
Laurent Gauthier ◽  
Don C. Wiley ◽  
Kai W. Wucherpfennig
Keyword(s):  
Crystal Structure ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Peptide Binding ◽  
Cell Receptor ◽  
Side Chain ◽  
Aromatic Side Chain ◽  
Leukocyte Antigen ◽  
Receptor Recognition ◽  
Peptide Binding Site

Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of MBP peptide that are important for T cell receptor recognition are prominent, solvent exposed residues in the crystal structure. A distinguishing feature of the HLA-DR2 peptide binding site is a large, primarily hydrophobic P4 pocket that accommodates a phenylalanine of the MBP peptide. The necessary space for this aromatic side chain is created by an alanine at the polymorphic DRβ 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases.

scholarly journals Myelin basic protein enhances axonal regeneration from neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengjian Yan ◽  
Lei Chu ◽  
Xiaojiong Jia ◽  
Lu Lin ◽  
Si Cheng
Keyword(s):  
Myelin Basic Protein ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Axonal Regeneration ◽  
Neural Progenitor Cells ◽  
Basic Protein ◽  
Neural Progenitor ◽  
Dependent Manner ◽  
Cord Injury

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

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