Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.

Phage displayed random peptide libraries were used to discover peptides which functionally mimic the monosaccharide glucose by screening these libraries against glucose-specific lectins. Although the screening of phage display libraries against single lectins has been previously reported, debate exi...

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Bibliographic Details
Main Author: Yu, Limin.
Other Authors: Brendan Patrick Orner
Format: Thesis
Language:English
Published: 2009
Subjects:
Online Access:http://hdl.handle.net/10356/18861
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author Yu, Limin.
author2 Brendan Patrick Orner
author_facet Brendan Patrick Orner
Yu, Limin.
author_sort Yu, Limin.
collection NTU
description Phage displayed random peptide libraries were used to discover peptides which functionally mimic the monosaccharide glucose by screening these libraries against glucose-specific lectins. Although the screening of phage display libraries against single lectins has been previously reported, debate exists whether the resulting peptides are indeed true sugar mimics or merely act as ligands for the targeted lectin. As part of a larger project to establish general rules for peptide and peptidomimetic-based sugar mimicry, we have screened two phage display libraries (“C-X7-C” and “X12”) against a series of three glucose-binding plant lectins: Concanavalin A (Con A), Pisum Sativum Agglutinin (PSA), and Lens Culinaris Agglutinin (LCA), so as to discover ligands that bind ALL THREE lectins and therefore could act as true functional sugar mimics. Because screening for sets of targets is a novel strategy, screens were performed in a number of optimized formats. The resulting peptide CSPIYKDTC strongly bound to Con A at the sugar binding site and bound weakly to LCA and PSA, indicating that it may be a functionally mimicking glucose. General rules for peptide and peptidomimetic-based sugar mimicry was established. It is hoped that it is possible to employ a similar strategy to find mimics of other monosaccarides, such as mannose )Man) or galactose (Gal) or more complex carbonhydrates.
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spelling ntu-10356/188612023-02-28T23:56:22Z Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries. Yu, Limin. Brendan Patrick Orner School of Physical and Mathematical Sciences DRNTU::Science::Chemistry::Organic chemistry::Carbohydrates Phage displayed random peptide libraries were used to discover peptides which functionally mimic the monosaccharide glucose by screening these libraries against glucose-specific lectins. Although the screening of phage display libraries against single lectins has been previously reported, debate exists whether the resulting peptides are indeed true sugar mimics or merely act as ligands for the targeted lectin. As part of a larger project to establish general rules for peptide and peptidomimetic-based sugar mimicry, we have screened two phage display libraries (“C-X7-C” and “X12”) against a series of three glucose-binding plant lectins: Concanavalin A (Con A), Pisum Sativum Agglutinin (PSA), and Lens Culinaris Agglutinin (LCA), so as to discover ligands that bind ALL THREE lectins and therefore could act as true functional sugar mimics. Because screening for sets of targets is a novel strategy, screens were performed in a number of optimized formats. The resulting peptide CSPIYKDTC strongly bound to Con A at the sugar binding site and bound weakly to LCA and PSA, indicating that it may be a functionally mimicking glucose. General rules for peptide and peptidomimetic-based sugar mimicry was established. It is hoped that it is possible to employ a similar strategy to find mimics of other monosaccarides, such as mannose )Man) or galactose (Gal) or more complex carbonhydrates. Master of Science 2009-07-20T07:27:57Z 2009-07-20T07:27:57Z 2008 2008 Thesis http://hdl.handle.net/10356/18861 en 84 p. application/pdf
spellingShingle DRNTU::Science::Chemistry::Organic chemistry::Carbohydrates
Yu, Limin.
Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.
title Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.
title_full Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.
title_fullStr Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.
title_full_unstemmed Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.
title_short Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.
title_sort discovery of glucose specific peptide based carbohydrate mimics using phage displayed random peptide libraries
topic DRNTU::Science::Chemistry::Organic chemistry::Carbohydrates
url http://hdl.handle.net/10356/18861
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