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dc.contributor.advisorKamer, Paul (Paul C. J.)
dc.contributor.authorPopa, Gina
dc.coverage.spatial215en_US
dc.date.accessioned2011-04-21T14:08:31Z
dc.date.available2011-04-21T14:08:31Z
dc.date.issued2010
dc.identifieruk.bl.ethos.552485
dc.identifier.urihttp://hdl.handle.net/10023/1836
dc.description.abstractDevelopment of selective artificial metalloenzymes by combining the biological concepts for selective recognition with those of transition metal catalysis has received much attention during the last decade. Targeting covalent incorporation of organometallic catalysts into proteins, we explored site-selective covalent coupling of phosphane and N–containing ligands. The successful approach for incorporation of phosphane ligands we report herein consists of site-specific covalent coupling of a maleimide functionalized hydrazide into proteins, followed by coupling of aldehyde functionalized phosphanes via a hydrazone linkage. Site selective incorporation of N–containing ligands was obtained by coupling maleimide functionalized N–ligands to proteins via Michael addition to the maleimide double bond. These two methods can be easily applied to virtually any protein displaying a single reactive cysteine and allows a wide range of possibilities in terms of cofactor design. Site-specific covalent incorporation of transition metal complexes of phosphane ligands into proteins was successfully obtained. The success of the approach is influenced by several factors like the metal precursor, the phosphane type and the protein scaffold. Metal complexes of 5–maleimido–1,10–phenanthroline modified proteins were formed in situ, via addition of a metal precursor to the phenanthroline modified proteins or by coupling preformed metal complexes to proteins via Michael addition of the thiol group from a cysteine residue to the maleimide double bond of the N-ligand. These successful coupling methods enable the use of a wide range of protein structures as templates for the preparation of artificial transition metalloenzymes, which opens the way to full exploration of the power of selective molecular recognition of proteins in transition metal catalysis.en_US
dc.language.isoenen_US
dc.publisherUniversity of St Andrews
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subjectArtificial metalloenzymesen_US
dc.subject.lccQP601.7P7
dc.subject.lcshMetalloenzymesen_US
dc.subject.lcshProteins--Chemical modificationen_US
dc.subject.lcshMolecular recognitionen_US
dc.subject.lcshTransition metal catalystsen_US
dc.titleDevelopment of artificial metalloenzymes via covalent modification of proteinsen_US
dc.typeThesisen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US


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Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported
Except where otherwise noted within the work, this item's license for re-use is described as Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported