Mehrfache orthogonale Konjugationen mit Molekülgerüsten: Anwendung in der chemischen Biologie und Wirkstoff‐Forschung

Abstract

Heteropolyfunktionelle Molekülgerüste, die sich sequenzielle Klick-Reaktionen zunutze machen, werden eine bedeutende Rolle in den Bereichen der chemischen Biologie und chemisch aktivierten Biotherapeutika, der so genannten "Chemologics" spielen. Dieser Kurzaufsatz fasst die bestehenden Synthesetechniken zusammen und verdeutlicht das beträchtliche Potenzial, das dieses Fachgebiet birgt.Abbildung 1. Difunktioneller Vernetzer Sulfo-SBED 1.

Oxime Ligation: A Chemoselective Click‐Type Reaction for Accessing Multifunctional Biomolecular Constructs

“…Oxime ligation can be used in conjunction with other click‐type reactions for preparing heterotopic multivalent bioconjugates 42–43. Combinations, such as oxime–thiol– CuAAC,43a,c, 44 and oxime–maleimide–CuAAC44 have been reviewed 43b. Dumy and co‐workers recently combined oxime ligation with CuAAC in order to prepare heterotopic multivalent peptide conjugates (45–72 % yield)45 and glycoconjugates 46.…”

Patchwork Protein Chemistry: A Practitioner's Treatise on the Advances in Synthetic Peptide Stitchery

“…For excellent reviews on further conjugates/ligation techniques beyond the scope (peptide/protein constructs through chemical synthesis by solid-phase/multiple ligation) of this contribution, see, for example, refs. [67] and [235]- [238]. [b] Similar endeavors have been reported for Ag + condensations by, for example, Tam et al (on TentaGel), [239] interestingly through entropic rather than enthalpic activation, due to Ag + -assisted coordination.…”

“…In brief, the original thioester strategy (not to be confused with the above thioester condensation) was followed by a multitude of related approaches, such as haloacetyl-based [53,54] (Scheme 2 C) or maleimidocaproyl-based (MIC-based, [55] Scheme 2 K) alkylation of thiol groups to yield thioethers, directed generation of disulfide bridges (Scheme 2 A), [56] together with the formation either of hydrazones and oximes (Scheme 2 E), [57,58] or of thiazolidines and oxazolidines (Scheme 2 G). [59,60] Through extensive crosstalk with the chemical biology field, the many labeling/ crosslinking techniques [61,62] for conjugation studies generated a wealth of ligation chemistries, [63][64][65][66][67] with procedures based on, for example, squarate/squaric acid, [68,69] quadricyclane [70] or tetrazine [71][72][73] (not shown in Scheme 2), alongside the use of DNA-templated reactions for similar purposes [74] and furan-triggering efforts from our own group. [75] The variety and recent popularity of strain-promoted cycloadditions [76,77] -including SPAAC (Scheme 2 N; strain-promoted alkyne-azide cycloaddition), SPANC (strain-promoted alkyne-nitrone cycloaddition), SPANOC (strain-promoted alkyne-nitrile oxide cycloaddition), [78] and SPIEDAC (strain-promoted inverse-electron demand Diels-Alder cycloaddition)-rely on the particular bioorthogonality of Diels-Alder-type pericyclization (Scheme 2 M) [79,80] and the click chemistry concept in general.…”

Biomolecular Assemblies Combining Two Orthogonal Copper‐Mediated Ligations in a One‐Pot Reaction

“…Although the use of orthogonal "click" reactions has provedt ob ep articularly useful, [1] the subjectr emains topical. The development of as trategy combining several orthogonal ligations is highly desirable.…”

“…Although the use of orthogonal "click" reactions has provedt ob ep articularly useful, [1] the subjectr emains topical. The major barriers to the chemical synthesis of these systems result from their high molecular weight and from the tricky purificationo ft heir intermediates.…”