Conformational analysis of O-linked glycopeptides related to enkephalin and nuclear pore proteins

Persistent Link:
http://hdl.handle.net/10150/284116
Title:
Conformational analysis of O-linked glycopeptides related to enkephalin and nuclear pore proteins
Author:
Kriss, Caroline Theresa
Issue Date:
1999
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The effect of O-linked glycosylation on peptide conformation has been studied in pursuit of understanding one of the natural roles of carbohydrates, and with an interest in drug design. Solution conformations were analyzed using a combination of NMR, molecular modeling, and kinetics techniques. Variations in peptide sequence, carbohydrate, and stereochemistry of linkage were made. Glycosylation of enkephalin analogs at the Ser⁶ position of the sequence Tyr-c-[D-cys-Gly-Phe-D-cys]-Ser-Gly-CONH₂ with a glucose moiety affected only the exocyclic portion of the molecule. An α-linkage constrained the carbohydrate and lessened the impact on peptide conformation, when compared to a β-linkage. Glycosylation of nuclear pore protein models of the sequence c-[Cys-Ser-Pro-Ser-Thr-Cys] at the Ser⁴ position increased turn formation irrespective of carbohydrate identity or linkage. Glycosylation of the uncyclic form of this sequence at Ser⁴ demonstrated no conformational differences. Flexibility of the unglycosylated sequence is paramount in determining the potential impact of glycosylation since two completely different effects are observed for glycosylation of the cyclic and uncyclic sequence.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Chemistry, Biochemistry.; Chemistry, Organic.; Biophysics, General.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Polt, Robin L.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleConformational analysis of O-linked glycopeptides related to enkephalin and nuclear pore proteinsen_US
dc.creatorKriss, Caroline Theresaen_US
dc.contributor.authorKriss, Caroline Theresaen_US
dc.date.issued1999en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe effect of O-linked glycosylation on peptide conformation has been studied in pursuit of understanding one of the natural roles of carbohydrates, and with an interest in drug design. Solution conformations were analyzed using a combination of NMR, molecular modeling, and kinetics techniques. Variations in peptide sequence, carbohydrate, and stereochemistry of linkage were made. Glycosylation of enkephalin analogs at the Ser⁶ position of the sequence Tyr-c-[D-cys-Gly-Phe-D-cys]-Ser-Gly-CONH₂ with a glucose moiety affected only the exocyclic portion of the molecule. An α-linkage constrained the carbohydrate and lessened the impact on peptide conformation, when compared to a β-linkage. Glycosylation of nuclear pore protein models of the sequence c-[Cys-Ser-Pro-Ser-Thr-Cys] at the Ser⁴ position increased turn formation irrespective of carbohydrate identity or linkage. Glycosylation of the uncyclic form of this sequence at Ser⁴ demonstrated no conformational differences. Flexibility of the unglycosylated sequence is paramount in determining the potential impact of glycosylation since two completely different effects are observed for glycosylation of the cyclic and uncyclic sequence.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectChemistry, Biochemistry.en_US
dc.subjectChemistry, Organic.en_US
dc.subjectBiophysics, General.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorPolt, Robin L.en_US
dc.identifier.proquest9927488en_US
dc.identifier.bibrecord.b3956647xen_US
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