Article

Encouraging Progress in the omega-Aspartylation of Complex Oligosaccharides as a General Route to beta-N-Linked Glycopolypeptides

Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, United States.
Journal of the American Chemical Society (Impact Factor: 11.44). 02/2011; 133(5):1597-602. DOI: 10.1021/ja110115a
Source: PubMed

ABSTRACT Described herein is a method for the joining of complex peptides to complex oligosaccharides via an N-linkage. The ω-aspartylation is conducted by coupling fully deprotected glycosylamine with a peptide containing a unique thioacid at the ω-aspartate carboxyl. In the presence of HOBT, under conditions that, in principle, allow for oxidation, complex components are combined in encouraging yields to produce structurally and stereochemically defined N-linked glycopolypeptides wherein the carbohydrate domain can be quite complex. Various mechanisms for oxidative coupling are proposed.

0 Bookmarks
 · 
151 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The synthesis of polypeptides on solid phase via mediation by isonitriles is described. The acyl donor is a thioacid, which presumably reacts with the isonitrile to generate a thio-formimidate carboxylate mixed anhydride intermediate. Applications of this chemistry to reiterative solid-phase peptide synthesis as well as solid-phase fragment coupling are described.
    Proceedings of the National Academy of Sciences 07/2013; DOI:10.1073/pnas.1310431110 · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thioester-mediated peptide bond formation has recently garnered a lot of attention, most notably in its relevance to condensation of large peptide fragments. Herein, a simple and general ligation method for the preparation of linear and cyclic peptides, starting from peptide thioester, mainly p-chlorophenyl, precursors is reported. The inherent advantages of this method are the low epimerization, reduced dimerization, use of mild reaction conditions, and elimination of superfluous coupling reagents.
    Organic Letters 07/2014; 16(15). DOI:10.1021/ol501669n · 6.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thioacids are recently gaining momentum due to their versatile reactivity. The reactivity of thioacids has been widely explored in the selective amide/peptide bond formation. Thioacids are generally synthesized from the reaction between activated carboxylic acids such as acid chlorides, active esters etc. and Na2S, H2S, or NaSH. We sought to investigate whether the versatile reactivity of the thioacids can be tuned for the conversion of carboxylic acids into corresponding thioacids in the presence of NaSH. Herein, we are reporting, thioacetic acid and NaSH mediated synthesis of N-protected amino thioacids from the corresponding N-protected amino acids, oxidative dimerization of thioacids, crystal conformations of thioacid oxidative dimers and the utility of thioacids and oxidative dimers in peptide synthesis. Results suggest that peptides can be synthesized without using standard coupling agents.
    The Journal of Organic Chemistry 02/2014; 79(6). DOI:10.1021/jo402872p · 4.64 Impact Factor

Preview

Download
1 Download
Available from