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A Convergent Synthesis of Homogeneous Reducible Polypeptides
Journal article   Peer reviewed

A Convergent Synthesis of Homogeneous Reducible Polypeptides

Mark D Ericson and Kevin G Rice
Tetrahedron letters, Vol.54(35), pp.4746-4748
08/28/2013
DOI: 10.1016/j.tetlet.2013.06.118
PMCID: PMC3908824
PMID: 24493905

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Abstract

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 numerous barriers for efficacious gene delivery.
acetamidomethyl thiazolidine convergent synthesis Reducible polypeptides cysteine

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