Tuning of Structure and Function through Haloarene- and Phenanthroline-Based Peptide Stapling

Erik Fumi

Tuning of Structure and Function through Haloarene- and Phenanthroline-Based Peptide Stapling

Erik Fumi

Abstract

Two peptide stapling methodologies for the introduction of rigid, aromatic linkers have been developed in the scope of this thesis. The first of the two stapling techniques involves the bis-arylation of two cysteines via SNArreaction with different haloarenes. The careful choice of substitution pattern in the haloarenes enables the stapling to take place in ortho-, meta-, or para- configuration, thus allowing for the introduction of different measures of conformational strain in the stapled peptide. This method has been shown to be an effective way of modulating bioactivity in melanocortin receptor agonists.The second peptide stapling method ology entails the introduction of a phenanthroline chelator via intermolecular lactamisation. This method has been shown to confer selective chelation properties to a set of stapled model peptides. The cuprous complexes of the stapled peptides have furthermore proven to be effective small molecule nucleases, displaying potent catalytic activity in an aqueous environment.

Original language	English

Publisher	Department of Chemistry, Faculty of Science, University of Copenhagen
Publication status	Published - 2019

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title = "Tuning of Structure and Function through Haloarene- and Phenanthroline-Based Peptide Stapling",

abstract = "Two peptide stapling methodologies for the introduction of rigid, aromatic linkers have been developed in the scope of this thesis. The first of the two stapling techniques involves the bis-arylation of two cysteines via SNArreaction with different haloarenes. The careful choice of substitution pattern in the haloarenes enables the stapling to take place in ortho-, meta-, or para- configuration, thus allowing for the introduction of different measures of conformational strain in the stapled peptide. This method has been shown to be an effective way of modulating bioactivity in melanocortin receptor agonists.The second peptide stapling method ology entails the introduction of a phenanthroline chelator via intermolecular lactamisation. This method has been shown to confer selective chelation properties to a set of stapled model peptides. The cuprous complexes of the stapled peptides have furthermore proven to be effective small molecule nucleases, displaying potent catalytic activity in an aqueous environment.",

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T1 - Tuning of Structure and Function through Haloarene- and Phenanthroline-Based Peptide Stapling

AU - Fumi, Erik

PY - 2019

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N2 - Two peptide stapling methodologies for the introduction of rigid, aromatic linkers have been developed in the scope of this thesis. The first of the two stapling techniques involves the bis-arylation of two cysteines via SNArreaction with different haloarenes. The careful choice of substitution pattern in the haloarenes enables the stapling to take place in ortho-, meta-, or para- configuration, thus allowing for the introduction of different measures of conformational strain in the stapled peptide. This method has been shown to be an effective way of modulating bioactivity in melanocortin receptor agonists.The second peptide stapling method ology entails the introduction of a phenanthroline chelator via intermolecular lactamisation. This method has been shown to confer selective chelation properties to a set of stapled model peptides. The cuprous complexes of the stapled peptides have furthermore proven to be effective small molecule nucleases, displaying potent catalytic activity in an aqueous environment.

AB - Two peptide stapling methodologies for the introduction of rigid, aromatic linkers have been developed in the scope of this thesis. The first of the two stapling techniques involves the bis-arylation of two cysteines via SNArreaction with different haloarenes. The careful choice of substitution pattern in the haloarenes enables the stapling to take place in ortho-, meta-, or para- configuration, thus allowing for the introduction of different measures of conformational strain in the stapled peptide. This method has been shown to be an effective way of modulating bioactivity in melanocortin receptor agonists.The second peptide stapling method ology entails the introduction of a phenanthroline chelator via intermolecular lactamisation. This method has been shown to confer selective chelation properties to a set of stapled model peptides. The cuprous complexes of the stapled peptides have furthermore proven to be effective small molecule nucleases, displaying potent catalytic activity in an aqueous environment.

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M3 - Ph.D. thesis

BT - Tuning of Structure and Function through Haloarene- and Phenanthroline-Based Peptide Stapling

PB - Department of Chemistry, Faculty of Science, University of Copenhagen

ER -

Tuning of Structure and Function through Haloarene- and Phenanthroline-Based Peptide Stapling

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