The Staudinger Ligation—A Gift to Chemical Biology

Abstract

Although the reaction between an azide and a phosphane to form an aza-ylide was discovered by Hermann Staudinger more than 80 years ago and has found widespread application in organic synthesis, its potential as a highly chemoselective ligation method for the preparation of bioconjugates has been recognized only recently. As the two reaction partners are bioorthogonal to almost all functionalities that exist in biological systems and react at room temperature in an aqueous environment, the Staudinger ligation has even found application in the complex environment of living cells. Herein we describe the current state of knowledge on this reaction and its application both for the preparation of bioconjugates and as a ligation method in chemical biology.

Porous polymer particles—A comprehensive guide to synthesis, characterization, functionalization and applications

“…In addition to amidation, several highly efficient esterification strategies are also well established [372]. Various other peptide ligation strategies such as native chemical ligation [373] and Staudinger ligation [374] are well described in literature [375] but are kept out of the scope of this review.…”

Diels–Alder Ligation of Peptides and Proteins

“…[42] In just few years after its establishment, the Staudinger ligation approach has proved to be a valuable tool for the preparation of bioconjugates in vitro and for the targeting of biomolecules in the complex environment of living cells. [43] Furthermore, approaches to find a traceless Staudinger ligation method, where a phosphane ligand is cleaved by hydrolysis thus leaving a native bond at the ligation site, are currently under development. [44][45] Although the Staudinger ligation can potentially be applied for noninvasive imaging and therapeutic targeting, [46] the reaction has some drawbacks.…”

N-Myristoyl transferase-mediated protein labelling in vivo

“…14 Here we report this work in full, and extend the scope to encompass transferasemediated in vivo production of alkynyl-tagged proteins and 50 subsequent bioorthogonal labelling with [3 + 2] azide-alkyne cycloaddition ('click' chemistry). 4 …”

“…In each case, an acid bearing the appropriate capture group (pent-4-ynoic acid 10, 4-azidobutyric acid 11 or 3-(diphenylphosphino)-4-(methoxycarbonyl) benzoic acid 12) 40 was preactivated with HATU and coupled in 4-fold excess relative to resin loading. Subsequent cleavage (95% aqueous TFA) and purification by RP-HPLC afforded the corresponding capture reagents bearing an azide (13), alkyne (14) or triarylphosphine (15) moiety in good overall yield. Expression constructs for CaNMT under ampicillin selection and PfARF1 under kanamycin selection were 50 co-transformed into E. coli BL21 (DE3) competent cells, and induced for 4 hours at 37 °C in the presence of 1 mM IPTG together with 0.5 mM 3 or 4.…”