A Solid Support-Based Synthetic Strategy for the Site-Selective Functionalization of Peptides with Organometallic Half-Sandwich Moieties |
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Authors: | Dr. Dianna Truong Dr. Nelson Y. S. Lam Dr. Meder Kamalov Mie Riisom Dr. Stephen M. F. Jamieson Prof. Paul W. R. Harris Prof. Margaret A. Brimble Prof. Nils Metzler-Nolte Prof. Christian G. Hartinger |
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Affiliation: | 1. School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142 New Zealand;2. Maurice Wilkins Centre for Biodiscovery, University of Auckland, Private Bag 92019, Auckland, 1142 New Zealand;3. Faculty of Chemistry and Biochemistry, Ruhr University Bochum, Bochum, 44801 Germany |
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Abstract: | The number of donor atoms available on peptides that can competitively coordinate to metal centers renders the site-selective generation of advanced metal-peptide conjugates in high purity a challenging venture. Herein, we present a transmetalation-based synthetic approach on solid support in which an imidazolium pro-ligand can be used to selectively anchor a range of transition metal half-sandwich complexes onto peptides in the presence of multiple coordinative motifs. Amenable to solid support, a range of N-terminus and/or lysine conjugated metal-peptide conjugates were obtained in high purity after cleavage from the resin. The metalated peptides were evaluated for their anticancer properties against human cancer cell lines. While no cytotoxic activity was observed, this platform has the potential to i) provide a pathway to site-selective peptide labelling, ii) be explored as a biorthogonal handle and/or iii) generate a new strategy for ligand design in transition metal catalysts. |
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Keywords: | carbene complexes on-resin synthesis peptide-metal conjugates peptide functionalization site selectivity |
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