Transition Metal-Promoted Arylation: An Emerging Strategy for Protein Bioconjugation

Abstract

Transition metal-mediated arylation chemistry is emerging as a powerful tool for the selective modification of native peptides and proteins, providing new opportunities in the field of bioconjugation. This highlight paper will summarize recent methodologies for the regio-and chemoselective arylation of select proteinogenic side chains and backbone amide N-H bonds within unprotected peptides and proteins. The importance of the metal-ligand complex in achieving tunable selectivity and the inherent benefits of arylation as a mode of covalent protein modification will be highlighted.

Arylation Chemistry for Bioconjugation

“…[47,52,[157][158][159][160][161] Metal-mediated arylation provides ac omplementary approach to S N Ar, and expands the scope of aryl modifications for peptides and proteins.Arepresentative selection of the existing organometallic approaches to biomolecule arylation is presented in the following sections. [47,52,[157][158][159][160][161] Metal-mediated arylation provides ac omplementary approach to S N Ar, and expands the scope of aryl modifications for peptides and proteins.Arepresentative selection of the existing organometallic approaches to biomolecule arylation is presented in the following sections.…”

“…Throughout this review,w ee mphasize the fundamental chemistry of arylative bioconjugation reactions.The complex nature of bioconjugates requires well-designed reagents and conditions as well as accurate product characterization prior to employing the resulting conjugates for biological applications.W eb elieve that there is no perfect bioconjugation reaction that fulfills all application needs.This review aims to complement other recent reviews on bioconjugation [42][43][44][45][46][47][48][49][50][51][52][53][54] and provide the reader with an expanded understanding of current bioconjugation techniques. We then describe the N-arylation of the e-amine of lysine.A rylation of other natural and unnatural amino acid side chains is also discussed with afocus on the umpolung arylation of selenocysteine and the palladium-catalyzed cross-coupling reactions for protein modification.…”

Arylierungschemie für die Biokonjugation

“…[47,52,[157][158][159][160][161] Die nukleophile aromatische Substitution (S N Ar) wird hierbei durch die Metall-vermittelteA rylierung ergänzt und das Einsatzgebiet der Arylmodifikationen von Peptiden und Proteinen entsprechend erweitert. [47,52,[157][158][159][160][161] Die nukleophile aromatische Substitution (S N Ar) wird hierbei durch die Metall-vermittelteA rylierung ergänzt und das Einsatzgebiet der Arylmodifikationen von Peptiden und Proteinen entsprechend erweitert.…”

“…Dieser Aufsatz verfolgt das Ziel, die Sichtweise anderer kürzlich erschienener Zusammenfassungen von Biokonjugationsmethoden [42][43][44][45][46][47][48][49][50][51][52][53][54] zu ergänzen und dem Leser ein breiteres Verständnis gegenwärtiger Biokonjugationstechniken zu vermitteln. Die vielgestaltige Beschaffenheit solche Biokonjugate bedarf maßgeschneiderter Reagentien und Bedingungen sowie genauer Charakterisierung der Produkte,b evor diese fürbiologische Anwendungen eingesetzt werden kçnnen.…”

Celebrating RACI and Academy of Science Awards

“…[5] Lara Malins, formerly a Ph.D. student at the University of Sydney under Professor Richard Payne and now a post-doc at UC San Diego, won the RACI's 2015 Cornforth Award for the best Ph.D. thesis and has contributed a highlight on 'TransitionMetal Promoted Arylation: An Emerging Strategy for Protein Bioconjugation'. [6] Christopher Gordon Newton, the Organic Division's inaugural 2015 Mander awardee for the Best PhD Thesis in Organic Chemistry, then a student in Professor Michael Sherburn's group and now a post-doc at the EPF Lausanne, has contributed a review together with E. G. Mackay on 'Masked Ketenes as Dienophiles in the Diels-Alder Reaction'. [7] Jonathan George (University of Adelaide) was awarded the Organic Division's Beckwith Lectureship for 2015 and has contributed a research communication with co-workers K. K. W. Kuan, and A. M. C. Hirschvogel entitled 'A Biomimetic Synthetic Approach to the Frondosins'.…”