Defining peptide structure with metathesis.
type: CreativeWork
description: Understanding protein structure and function is central for the development of therapeutics for the treatment of diseases and also novel biocompatible materials. Herein describes studies on the control of peptide structure and function through synthetic modifications, for the synthesis of novel enzyme inhibitors and biomaterials, primarily using olefin metathesis chemistry. Metathesis is chosen for the manipulation of peptide structure in order to induce conformational constraint in novel macrocyclic peptidomimetic inhibitors and to develop novel hydrogel matrices, which are of importance in the advancement of the pharmaceutical and medical industries. The realization that enzymes bind their substrates in an extended β-stranded conformation has led to the development of inhibitors that mimic this bioactive conformation. The controlled organization of secondary structures in peptides by conformational constraint has been utilized to design two novel series of macrocyclic inhibitors, which are constrained by the P₁ and P₃ residues or the P₂ and P₄ residues using ring closing metathesis (RCM). These inhibitors contain a pyrrole group in the peptide backbone, thereby decreasing the peptidic nature of these inhibitors minimising susceptibility to proteolysis, while maintaining the appropriate geometry for inhibitor binding. The corresponding P₁-P₃ and P₁-P₄ acyclic inhibitors are designed and synthesized to provide an insight into the importance of cyclisation on the potency of inhibition against serine and cysteine protease. The macrocyclic and acyclic inhibitors synthesized are assayed against a series of cysteine (calpain and cathepsin) and serine proteases (α-chymotrypsin, human leukocyte elastase and trypsin). These enzyme assays analyse the efficacy of the inhibitors against the enzymes tested. The potency of the inhibitors against the aforementioned proteases provides an insight into the effect of cyclisation, ring size and introduction of aryl groups into the rin…
abstract: Understanding protein structure and function is central for the development of therapeutics for the treatment of diseases and also novel biocompatible materials. Herein describes studies on the control of peptide structure and function through synthetic modifications, for the synthesis of novel enzyme inhibitors and biomaterials, primarily using olefin metathesis chemistry. Metathesis is chosen for the manipulation of peptide structure in order to induce conformational constraint in novel macrocyclic peptidomimetic inhibitors and to develop novel hydrogel matrices, which are of importance in the advancement of the pharmaceutical and medical industries. The realization that enzymes bind their substrates in an extended β-stranded conformation has led to the development of inhibitors that mimic this bioactive conformation. The controlled organization of secondary structures in peptides by conformational constraint has been utilized to design two novel series of macrocyclic inhibitors, which are constrained by the P₁ and P₃ residues or the P₂ and P₄ residues using ring closing metathesis (RCM). These inhibitors contain a pyrrole group in the peptide backbone, thereby decreasing the peptidic nature of these inhibitors minimising susceptibility to proteolysis, while maintaining the appropriate geometry for inhibitor binding. The corresponding P₁-P₃ and P₁-P₄ acyclic inhibitors are designed and synthesized to provide an insight into the importance of cyclisation on the potency of inhibition against serine and cysteine protease. The macrocyclic and acyclic inhibitors synthesized are assayed against a series of cysteine (calpain and cathepsin) and serine proteases (α-chymotrypsin, human leukocyte elastase and trypsin). These enzyme assays analyse the efficacy of the inhibitors against the enzymes tested. The potency of the inhibitors against the aforementioned proteases provides an insight into the effect of cyclisation, ring size and introduction of aryl groups into the rin…
author: Chua, Krystle Chia Hsien
keywords: peptide; metathesis; inhibitor; assays; hydrogels
date published: 2013
date modified: 2026-07-24T00:50:56Z
provider: University of Adelaide
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Adelaide

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2440/92334