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Towards the Development of New Bioconjugation Strategies for Peptides and Proteins

Abstract

Incorporation of inorganic-based moieties into biological molecules can engender new properties and applications. In this thesis, two projects are described that aim to introduce new inorganic motifs into peptides. The first project describes attempts to incorporate palladium ion into the active site of the naturally-occurring metalloprotein Sso10b2 (from the archaeon Sulfolobus solfataricus). Since the native protein contains zinc, it cannot be obtained using recombinant technologies, since subsequent metal exchange requires harsh conditions. Using standard solid-phase peptide synthesis, we synthesized peptide fragments that would directly interact with Pd(II), and studied the metallation process via liquid chromatography-mass spectrometry and circular dichroism. The second project describes a new cysteine bioconjugation technique using organometallic boron-cluster reagents. A platinum-boryl complex was used to selectively label the cysteine residue of an unprotected peptide with a carborane, via reductive elimination mechanism. These carborane labels will ultimately serve as tags for Raman microscopy, allowing us to track our target peptides within cells.

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