Macrocyclization of glucagon-like peptide (GLP-1) by thiol-ene reaction

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Publication Type honors thesis
School or College College of Science
Department Chemistry
Faculty Mentor Danny Hung-Chieh Chou
Creator Zurbuchen, Rudi
Title Macrocyclization of glucagon-like peptide (GLP-1) by thiol-ene reaction
Year graduated 2016
Date 2016-05
Description Macrocyclization of peptides helps maintain a stable alpha helical structure using a conformational constraining staple. One such peptide, glucagon-like peptide-1 (GLP-1), is a 37 amino acid peptide agonist for the GLP-1 receptor and has the ability to lower blood glucose levels and is responsible for postprandial insulin release. Natural GLP-1 is quickly degraded by the proteases dipeptidyl peptidase-IV (DPP-IV) and endopeptidase (NEP) 24.11, and therefore, analogues have been researched for potential therapeutic treatmen ts of Type 2 Diabetes (T2D). Stapling peptides increases the stability of the alpha helical conformation, native to peptides such as GLP-1. Some stapling techniques include a ring-closing olefin metathesis (RCM) and formation of a lactam bridge between side chains or the peptide backbone in a i, i+4 manner. An alternative macrocyclization technique is the two component thiolene reaction. This reaction does not use unnatural amino acids or toxic metal catalysts, making this reaction useful under a variety of conditions. Additionally, since this process does not require post synthetic modification, the peptides has the potential to use a wide varieties of linkers to accomplish cyclization. This project determined and applied a new method to staple analogues in GLP-1 with cysteine residues to carry out the thiol-ene reaction for peptide cyclization. GLP-1 mono stapling was achieved for three GLP-1 cysteine substituted analogues and two staples were accomplished for one GLP-1 cysteine substituted analogue.
Type Text
Publisher University of Utah
Subject Peptide hormones - Receptors - Research; Ring formation (Chemistry) - Research; Macrocyndization; GLP-1; Swim kinematics; Pre-pulse inhibition
Language eng
Rights Management (c) Rudi Zurbuchen
Format Medium application/pdf
Format Extent 25,087 bytes
Identifier honors/id/64
Permissions Reference URL https://collections.lib.utah.edu/details?id=1318470
ARK ark:/87278/s6b02f4j
Setname ir_htoa
ID 205716
Reference URL https://collections.lib.utah.edu/ark:/87278/s6b02f4j