A novel, rationally designed lanthanoid chelating tag delivers large paramagnetic structural restraints for biomolecular NMR

Herein, a novel and rationally designedortho-substituted pyridine activator is reported that reacts rapidly and selectively with cysteine thiols. It forms reduction-stable conjugates and induces large pseudocontact shifts, residual dipolar couplings and paramagnetic relaxation enhancement on both ubiquitin S57C and human carbonic anhydrase II S50C constructs under physiological conditions.