N ‐Hydroxysuccinimide‐Modified Ethynylphosphonamidates Enable the Synthesis of Configurationally Defined Protein Conjugates

Herein, the application of N ‐hydroxysuccinimide‐modified phosphonamidate building blocks for the incorporation of cysteine‐selective ethynylphosphonamidates into lysine residues of proteins, followed by thiol addition with small molecules and proteins, is reported. It is demonstrated that the building blocks significantly lower undesired homo‐crosslinking side products that can occur with commonly applied succinimidyl 4‐( N...