A Convergent Synthesis of Homogeneous Reducible Polypeptides.
The convergent syntheses of homogeneous disulfide cross-linked polypeptides are reported. Reducible polypeptides were synthesized containing four and eight dodecapeptides in two and three linear conjugation steps. Critical for the convergent methodology was the use of orthogonally protected cysteines as either acetamidomethyl (Acm) or Fmoc-thiazolidine (Thz). Both groups could be selectively deprotected with silver trifluoromethanesulfonate in the presence of internal disulfide bonds using TFA and aqueous conditions, respectively. This approach allows for large, reducible polypeptides to be synthesized in efficient yields and minimizes the number of conjugation steps, allowing the development and optimization of gene delivery polypeptides containing multiple peptide components necessary to overcome the numerousin vivobarriers for efficacious gene delivery.
Division of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City IA 52242.
Mark D
MD
Ericson
Division of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City IA 52242.
Kevin G
KG
Rice
Reducible polypeptides; acetamidomethyl; convergent synthesis; cysteine; thiazolidine