Iterative reducible ligation to form homogeneous penicillamine cross-linked polypeptides

Mark D. Ericson, Kevin G. Rice

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2 Scopus citations


The syntheses of homogeneous penicillamine disulfide cross-linked polypeptides are reported. Dodecapeptides containing N-terminal, C-terminal, or N- and C-terminal Pen were serially ligated into 36 amino acid polypeptides linked through Cys-Pen, Pen-Cys, or Pen-Pen disulfide bonds. Critical to the syntheses was the incorporation of thiazolidine masked Cys and Pen as the N-terminal residues and selective hydrolysis with silver trifluoromethanesulfonate in acidic aqueous conditions to generate a free thiol for subsequent ligation. This approach allows the synthesis of homogeneous disulfide cross-linked polypeptides that have different reductive stabilities and have application in gene delivery by undergoing a tempered reductive triggered release of DNA.

Original languageEnglish (US)
Pages (from-to)3440-3443
Number of pages4
JournalTetrahedron Letters
Issue number26
StatePublished - Jun 26 2013
Externally publishedYes

Bibliographical note

Funding Information:
The authors gratefully acknowledge funding for this research by the NIH GM087653 , T32 GM008365 and a predoctoral fellowship from the American Foundation for Pharmaceutical Education (MDE) .


  • Gene delivery
  • Penicillamine
  • Reducible polypeptides
  • Thiazolidine


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