DTNP as a Gentle and Effective Method of Deprotection for Side-Chain Protectants on Commercially-Available Cys and Sec SPPS Derivatives

摘要

The use of cysteine (Cys) and selenocysteine (Sec) building blocks in solid phase peptide synthesis requires the judicious selection of orthogonal blocking protocol between standard Fmoc or Boc N~α protection and their reactive thiol and selenol sidechain functionalities. Many of the existing commercially-available Cys and Sec derivatives require relatively harsh conditions to effect the removal of their side chain protectants. In a previously-reported account by our research group [1], we introduced a gentler protocol for the removal of Acm and Mob S-and Se-protection using the conditions of 2,2'-dithiobis(5-nitropyridine) (DTNP) in a TFA/thioanisole solvent system. Based upon these initial successes, we have now expanded this study to include a comprehensive evaluation of these conditions to mediate the removal of many acid-stable commercially-available Cys and Sec side chain protectants.