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The Chemical Synthesis of the Collagenous Domain of the Hormone Adiponectin

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Abstract

As a first step towards the preparation of a functional biomolecule, a chemical synthesis of the collagenous domain of adiponectin is described. The 76 residue polypeptide (without post-translational modifications) could be assembled efficiently from smaller unprotected peptides using two native chemical ligation reactions followed by a reductive desulfurisation step. In turn, the polypeptides were synthesised in high purity by microwave enhanced solid phase synthesis.

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References

  • Allevi P, Paroni R, Ragusa A, Anastasia M (2004) Hydroxylysine containing glycoconjugates: an efficient synthesis of natural galactosylhydroxylysine (Gal-Hyl) and glucosylgalactosylhydroxylysine (Glu-Gal-Hyl) and of their (5S)-epimers. Tetrahedron Asymmetr 15:3139–3148

    Article  CAS  Google Scholar 

  • Blanco-Canosa JB, Dawson PE (2008) An efficient Fmoc-SPPS approach for the generation of thioester peptide precursors for use in native chemical ligation. Angew Chem Int Edit 47:6851–6855

    Article  CAS  Google Scholar 

  • Brik A, Harpaz Z, Siman P, Kumar KSA (2010) Protein synthesis assisted by native chemical ligation at leucine. ChemBioChem 11:1232–1235

    Article  PubMed  Google Scholar 

  • Chen YX, Mant CT, Hodges RS (2007) Preparative reversed-phase high-performance liquid chromatography collection efficiency for an antimicrobial peptide on columns of varying diameters (1 to 9.4 mm ID). J Chromatogr A 1140:112–120

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Wan Q, Yuan Y, Zhu J, Danishefsky SJ (2008) Native chemical ligation at valine: a contribution to peptide and glycopeptide synthesis. Angew Chem Int Ed Engl 47:8521–8524

    Article  PubMed  CAS  Google Scholar 

  • Crich D, Banerjee A (2007) Native chemical ligation at phenylalanine. J Am Chem Soc 129:10064–10065

    Article  PubMed  CAS  Google Scholar 

  • Dawson PE, Muir TW, Lewis IC, Kent SBH (1994) Synthesis of proteins by native chemical ligation. Science 266:776–779

    Article  PubMed  CAS  Google Scholar 

  • Diez JJ, Iglesias P (2010) The role of the novel adipocyte-derived protein adiponectin in human disease: an update. Mini Rev Med Chem 10:856–869

    Article  PubMed  CAS  Google Scholar 

  • Haase C, Rohde H, Seitz O (2008) Native chemical ligation at valine. Angew Chem Int Edit 47:6807–6810

    Article  CAS  Google Scholar 

  • Hackeng TM, Griffin JH, Dawson PE (1999) Protein synthesis by native chemical ligation: expanded scope by using straightforward methodology. Proc Natl Acad Sci USA 96:10068–10073

    Article  PubMed  CAS  Google Scholar 

  • Harris PWR, Brimble MA (2009) Synthesis of an arginine tagged [Cys(155)-Arg(180)] fragment of NY-ESO-1: elimination of an undesired by-product using ‘In House’ resins. Synth Stuttgart 20:3460–3466

    Article  Google Scholar 

  • Johnson ECB, Kent SBH (2006) Insights into the mechanism and catalysis of the native chemical ligation reaction. J Am Chem Soc 128:6640–6646

    Article  PubMed  CAS  Google Scholar 

  • Kent SBH (2009) Total chemical synthesis of proteins. Chem Soc Rev 38:338–351

    Article  PubMed  CAS  Google Scholar 

  • Kent SBH, Durek T, Torbeev VY (2007) Convergent chemical synthesis and high-resolution X-ray structure of human lysozyme. Proc Natl Acad Sci USA 104:4846–4851

    Article  PubMed  Google Scholar 

  • Matsuzawa Y (2010) Adiponectin: a key player in obesity related disorders. Curr Pharm Design 16:1896–1901

    Article  CAS  Google Scholar 

  • Pasunooti KK, Yang R, Vedachalam S, Gorityala BK, Liu CF et al (2009) Synthesis of 4-mercapto-l-lysine derivatives: potential building blocks for sequential native chemical ligation. Bioorg Med Chem Lett 19:6268–6271

    Article  PubMed  CAS  Google Scholar 

  • Pentelute BL, Kent SBH (2007) Selective desulfurization of cysteine in the presence of Cys(Acm) in polypeptides obtained by native chemical ligation. Org Lett 9:687–690

    Article  PubMed  CAS  Google Scholar 

  • Rohde H, Seitz O (2010) Ligation-desulfurization: a powerful combination in the synthesis of peptides and glycopeptides. Biopolymers 94:551–559

    Article  PubMed  CAS  Google Scholar 

  • Simpson F, Whitehead JP (2010) Adiponectin—it’s all about the modifications. Int J Biochem Cell Biol 42:785–788

    Article  PubMed  CAS  Google Scholar 

  • Villain M, Vizzavona J, Rose K (2001) Covalent capture: a new tool for the purification of synthetic and recombinant polypeptides. Chem Biol 8:673–679

    Article  PubMed  CAS  Google Scholar 

  • Wan Q, Danishefsky SJ (2007) Free-radical-based, specific desulfurization of cysteine: a powerful advance in the synthesis of polypeptides and glycopolypeptides. Angew Chem Int Ed 46:9248–9252

    Article  CAS  Google Scholar 

  • Wang Y, Xu AM, Knight C, Xu LY, Cooper GJS (2002) Hydroxylation and glycosylation of the four conserved lysine residues in the collagenous domain of adiponectin—potential role in the modulation of its insulin-sensitizing activity. J Biol Chem 277:19521–19529

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Lam KS, Yau MH, Xu A (2008) Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J 409:623–633

    Article  PubMed  CAS  Google Scholar 

  • Yan LZ, Dawson PE (2001) Synthesis of peptides and proteins without cysteine residues by native chemical ligation combined with desulfurization. J Am Chem Soc 123:526–533

    Article  PubMed  CAS  Google Scholar 

  • Yang R, Pasunooti KK, Li F, Liu XW, Liu CF (2009) Dual native chemical ligation at lysine. J Am Chem Soc 131:13592–13593

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank The Maurice Wilkins Centre for Molecular Biodiscovery for financial support.

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Authors and Affiliations

  1. School of Chemical Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, 23 Symonds St, Auckland, 1142, New Zealand

    Paul W. R. Harris & Margaret A. Brimble

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  1. Paul W. R. Harris
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  2. Margaret A. Brimble
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Correspondence to Paul W. R. Harris.

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Harris, P.W.R., Brimble, M.A. The Chemical Synthesis of the Collagenous Domain of the Hormone Adiponectin. Int J Pept Res Ther 18, 63–70 (2012). https://doi.org/10.1007/s10989-011-9279-3

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  • DOI: https://doi.org/10.1007/s10989-011-9279-3

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