Cyclometalated gold(iii) complexes for chemoselective cysteine modification via ligand controlled C–S bond-forming reductive elimination

Abstract

Modular assembly of cyclometalated gold(III) complexes by choosing appropriate bidentate C,N-donor ligands and ancillary ligands for chemoselective cysteine modification of peptides and proteins via C-S bond-forming reductive elimination has been achieved.

Cyclometalated AuIII Complexes for Cysteine Arylation in Zinc Finger Protein Domains: towards Controlled Reductive Elimination

“…[2] Thus, the past decade has witnessed new ways of tagging proteins with fluorophores or otherp robes based on palladium-mediated reactions that playedamajor role in moderno rganic synthesis, such as the Suzuki-Miyaura,M izoroki-Heck,a nd Sonogashira cross-couplingr eactions. [8] Under these conditions, the reaction did not stop at the gold-peptide adducts,b ut produced the arylated product resulting from CÀS reductivee limination.T he excellent chemoselectivity of the reactionw as further demonstrated in bioconjugationr eactions targeting the surface exposedc ysteine residue of serum albumin, with the aid of ad ansyl-linked Au III C^N derivative of A. [4] To address these limitations, efforts have been made to designt ransition-metal complexes of reduced fragilityi nt he biological milieu, including the use of palladium nanoparticles.…”

“…Recently,p romising strategies have been developedt oa pply transition-metal complexes to bioconjugation. [6,7] Following the strategy of introducing aryl moieties in proteins with the aid of aryl transition-metal reagents, Wong and co-workersh avet ackledt he possibility of forming CÀSb onds by derivatizing the sulfhydryl group in cysteines, [8] as an alternative to the N-methylmaleimide cysteinel igation, given the lack of stability in physiological environments of the maleimide adducts. [2] Thus, the past decade has witnessed new ways of tagging proteins with fluorophores or otherp robes based on palladium-mediated reactions that playedamajor role in moderno rganic synthesis, such as the Suzuki-Miyaura,M izoroki-Heck,a nd Sonogashira cross-couplingr eactions.…”

Metallvermittelte Funktionalisierung natürlicher Peptide und Proteine: Biokonjugation mit Übergangsmetallen

“…[81] Die gleichen Autoren entdeckten außerdem die Anwendbarkeit dieser Reaktion zur chemoselektiven Modifikation an Lysinresten in Abwesenheit von Cysteinseitenketten. [87] Goldkomplexe besitzen überdies eine bemerkenswerte Toleranz gegenüber den verschiedensten funktionellen Gruppen. [82] Abbildung 10.…”

“…CysT hioalkoxyhydroxylierung von Allenen [33] Au RNase (14) 2.2 CysP hotoredox-Kreuzkupplung von Arylhalogeniden [25] Ni 9-mer-Peptid (1) 2.1 CysK upplung mit vorgeformten Arylmetallkomplexen [78,87] Au, Pd Antikçrper (150) 3.1,2 CysT hiol-S-H-Insertion von Diazoverbindungen [133] Rh TIM (27) 4 CysR eduktion & Metallierung an Disulfidzentren [190] Pt IgG (150) 5.5 CysC han-Lam-Kupplung mit 2-Nitroaryl boronsäuren [111] Ni B-Domäne aus Protein A(66) 3.5 Dha…”

Gold‐Catalyzed C–S Aryl‐Group Transfer in Zinc Finger Proteins

“…[29] Palladium(II) complexes can be used for cysteine conjugation (bioconjugation) reactions through arylgroup transfer and may find application in production of stapled peptides and antibody-drug conjugates. [31] This observation is further borne out in our studies noting the difference between nac and gSH. [31] This observation is further borne out in our studies noting the difference between nac and gSH.…”