Structural and immunological manifestations of racemization in myelin basic protein peptides

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)



First Committee Member

Eugene H. Man, Committee Chair


Myelin basic protein (MBP) from central nervous system myelin, undergoes racemization in situ, most rapidly at aspartyl and seryl residues. This protein is highly antigenic, producing experimental allergic encephalomyelitis (EAE) when injected into laboratory animals.Peptide (69-84) of guinea pig MBP, a most potent encephalitogen in Lewis rats, was chosen as the parent peptide in which to study how the racemization of aspartyl and/or seryl constituent residues affects its immunogenicity as well as its structural characteristics in solution as determined by nuclear magnetic resonance (NMR) spectroscopy.Results show that depending upon where in the primary sequence the D-residue substitution takes place, the outcome is either full encephalitogenicity for (69-84) DSer$\sp{70}$ or no disease induction for (69-84) DSer$\sp{75}$ and (69-84) DAsp$\sp‚.$The $\sp1$H NMR analyses indicate that there are similarities between (69-84) and (69-84) DSer$\sp{70}$ (chemical shifts, amide temperature coefficients) which are not shared by (69-84) DAsp$\sp‚.$ The encephalitogenic peptides exhibited an extended, highly flexible peptide backbone with little or no evidence of hydrogen bonding interactions, whereas in (69-84) DAsp$\sp‚,$ although having an extended peptide backbone, there are indications of hydrogen bonding interactions in solution.


Chemistry, Organic

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