Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides.

Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides. Research Abstract Details 

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Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides. Abstract Text:

Martin Viau,Myriam ,Ariane Sirois-Deslongchamps,Yvan Boulanger,Alain Fournier,Martin Viau,Myriam Létourneau,Ariane Sirois-Deslongchamps,Yvan Boulanger,Alain Fournier,

Many neurodegenerative diseases are related to an abnormal expansion of the CAG trinucleotide that produces polyglutamine segments in several proteins. However, the pathogenesis of these neurodegenerative states is not yet well understood. Thus, to evaluate the molecular mechanisms leading to those diseases, suitable research tools such as synthetic polyglutamine peptides are required. The synthesis and purification of such peptides are usually difficult because of poor solubility, which leads to low coupling and/or deblocking reactivity. After exploring many synthesis, solubilization and purification approaches, a protocol allowing the production of polyglutamines in good yield and high purity was developed. With this protocol, peptides of 10-30 glutamine residues were synthesized using a linear solid-phase strategy combined with a maximal side-chain protection scheme using fluorenylmethyloxycarbonyl (Fmoc) chemistry. After cleavage of the peptide from the polymeric support, the crude material was treated with glacial acetic acid and lyophilized. This treatment significantly improved the solubility of the polyglutamine peptides thus allowing their dissolution in aqueous conditions and purification through reverse-phase high performance liquid chromatography. These solubilization and purification conditions led to the formation of N-pyroglutamyl peptide derivatives that were easily isolated. These N-pyroglutamylated compounds also appear as useful research tools because data from the literature suggest that N-terminal modification of polyglutamine segments might play a role in their pathogenic properties.

Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides. Publishing Authors By Initials

M Viau,M ,A Sirois-Deslongchamps,Y Boulanger,A Fournier,M Viau,M Létourneau,A Sirois-Deslongchamps,Y Boulanger,A Fournier,

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Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biopolymers

VOLUME: 88

Page Numbers: 754-63

Journal Abbreviation: Biopolymers

ISSN: 0006-3525

DAY: 12

MONTH: 09

YEAR: 2007

Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides. Information

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LANGUAGE: eng

NlmUniqueID: 372525

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Grant and Affiliation Information for Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides.

AFFILIATION: Hôpital Saint-Luc du Centre Hospitalier de l'Université de Montréal, 1058 St-Denis, Montréal, QC, Canada H2X 3J4.

Country: United States

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MEDLINETA: Biopolymers

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