Rational design and study of peptide ligands for carbohydrates : applications in understanding bimolecular recognition and in targeting of biomolecules

Authors
Shastry, Divya Gowri
ORCID
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Other Contributors
Karande, Pankaj
Linhardt, Robert J.
McGown, Linda Baine
Cramer, Steven M.
Issue Date
2017-05
Keywords
Biochemistry and biophysics
Degree
PhD
Terms of Use
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
Full Citation
Abstract
Peptides as ligands in the targeting of carbohydrates may serve two purposes – to develop novel ligands that exhibit characteristics (like low molecular weight and production ease) amenable for application as well to promote understanding of carbohydrate biological recognition. Specifically, in regard to the latter purpose, peptides offer the possibility to study and exploit natural carbohydrate interactions as the basis for rational design. In this work, carbohydrate-binding peptides were rationally designed against the glycan polysialic acid (PSA), which appears in many interesting contexts, such as influencing nervous system development on neural progenitor cells and promoting tumor cell metastasis. The rational design approach employed through examination of PSA–protein interactions enabled molecular-level understanding of these natural PSA interactions and led to the development of PSA-binding peptides that may be used in biosensing and targeting applications, such as glycan-based targeting of stem cells for regenerative medicine. PSA-binding peptides were shown to demonstrate sequence-dependent specificity, thus leading to the development of rules for glycan recognition by engineered peptide ligands. Ultimately, principles learnt from this body of work may be extended to other carbohydrate systems, leading to such applications as small-molecule targeting of specific glycosylation patterns in healthcare contexts.
Description
May 2017
School of Science
Department
Biochemistry and Biophysics Program
Publisher
Rensselaer Polytechnic Institute, Troy, NY
Relationships
Rensselaer Theses and Dissertations Online Collection
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