Chemical synthesis of polar zipper peptides: motifs for potential protein association in inherited neurodegenerative diseases.
Syntheses of peptides containing contiguous repeats of glutamine or asparagine, related to sequences derived from proteins associated with neurodegenerative diseases, are described. Such homo-polymeric peptides are notoriously difficult to prepare due to the formation of aggregated structures during their solid phase synthesis. A novel approach using a randomized array of side chain protected and unprotected residues proved to be an effective strategy for preventing intermolecular peptide-chain association.
Johnson
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Medical Research Council, Laboratory of Molecular Biology, Cambridge, England, U.K.
D000595:Amino Acid Sequence; D001927:Brain Diseases / Q000235:genetics* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005973:Glutamine; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D007202:Indicators and Reagents; D017827:Machado-Joseph Disease / Q000378:metabolism; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013132:Spinocerebellar Degenerations / Q000378:metabolism
D007202:Indicators and Reagents; D009419:Nerve Tissue Proteins; D010455:Peptides; C095278:atrophin-1; D005973:Glutamine