From Cloudy to Clear: A Strategy to Resolve the Complex Structural Elucidation of Bicycle Drug Conjugate Zelenectide Pevedotin by NMR.

Zelenectide pevedotin is a Nectin-4 targeting Bicycle drug conjugate® (BDC®) that has fast track designation for the treatment of bladder, breast, and lung cancers. Its structure is highly complex and comprises a Bicycle connected to microtubule inhibitor monomethyl aurostatin-E (MMAE) via a molecular spacer and a cleavable linker. This provides a unique challenge in structural elucidation, and this report shows a strategy to overcome this using an incremental, nuclear magnetic resonance spectroscopy-based approach, which may be applied to complex structures of a similar nature.