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Iterative Reducible Ligation to form Homogeneous Penicillamine Cross-linked Polypeptides
Journal article   Peer reviewed

Iterative Reducible Ligation to form Homogeneous Penicillamine Cross-linked Polypeptides

Mark D Ericson and Kevin G Rice
Tetrahedron letters, Vol.54(26), pp.3440-3443
06/26/2013
DOI: 10.1016/j.tetlet.2013.04.086
PMCID: PMC3857801
PMID: 24347694
url
http://doi.org/10.1016/j.tetlet.2013.04.086View
Open Access

Abstract

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.
gene delivery thiazolidine penicillamine Reducible polypeptides

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