Synlett 2017; 28(15): 1913-1916
DOI: 10.1055/s-0036-1590795
© Georg Thieme Verlag Stuttgart · New York

Iminoboronate-Mediated Peptide Cyclization with Lysine Homologues

Kaicheng Li
Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA   Email:
Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA   Email:
› Author Affiliations
The financial support of this project is provided by the National Institutes of Health via grant GM102735
Further Information

Publication History

Received: 13 April 2017

Accepted after revision: 28 May 2017

Publication Date:
05 July 2017 (online)

Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis


Cyclic peptides are attracting attention of medicinal chemists due to their increased stability in biological milieu as well as improved target binding affinities. Our laboratory has recently reported a powerful cyclization strategy that takes advantage of the spontaneous and reversible conjugation of lysine and a designed amino acid AB3 to give iminoboronates. Herein we report that Dap, a short chain homologue of lysine, displays significantly higher propensity to form imino­boronates and consequently improves the efficiency of peptide cyclization. Importantly, the preferential conjugation of AB3 to Dap allows a facile synthesis of cyclic peptides with free lysine residues.

Supporting Information

  • References and Notes

  • 1 Baeriswyl V. Heinis C. ChemMedChem. 2013; 8: 377
  • 2 White CJ. Yudin AK. Nat. Chem. 2011; 3: 509
  • 3 Peraro L. Siegert TR. Kritzer JA. Methods Enzymol. 2016; 580: 303
  • 4 Malins LR. deGruyter JN. Robbins KJ. Scola PM. Eastgate MD. Ghadiri MR. Baran PS. J. Am. Chem. Soc. 2017; 139: 5233
  • 5 McCarver SJ. Qiao JX. Carpenter J. Borzilleri RM. Poss MA. Eastgate MD. Miller MM. MacMillan DW. C. Angew. Chem. Int. Ed. 2017; 56: 728
  • 6 Lawson KV. Rose TE. Harran PG. Proc. Natl. Acad. Sci., U.S.A. 2013; 110: E3753
  • 7 Cromm PM. Schaubach S. Spiegel J. Fürstner A. Grossmann TN. Waldmann H. Nat. Commun. 2016; 7: 11300
  • 8 Mendive-Tapia L. Preciado S. Garcia J. Ramon R. Kielland N. Albericio F. Lavilla R. Nat. Commun. 2015; 6: 7160
  • 9 Zhang J. Mulumba M. Ong H. Lubell WD. Angew. Chem. Int. Ed. 2017; 56: 6284
  • 10 Bowerman CJ. Nilsson BL. J. Am. Chem. Soc. 2010; 132: 9526
  • 11 Qian Z. Xu X. Amacher JF. Madden DR. Cormet-Boyaka E. Pei D. Angew. Chem. Int. Ed. 2015; 54: 5874
  • 12 Bandyopadhyay A. Gao J. J. Am. Chem. Soc. 2016; 138: 2098
  • 13 Cal PM. Vicente JB. Pires E. Coelho AV. Veiros LF. Cordeiro C. Gois PM. J. Am. Chem. Soc. 2012; 134: 10299
  • 14 Bandyopadhyay A. McCarthy KA. Kelly MA. Gao J. Nat. Commun. 2015; 6: 6561
  • 15 Lan Y. Langlet-Bertin B. Abbate V. Vermeer LS. Kong X. Sullivan KE. Leborgne C. Scherman D. Hider RC. Drake AF. Bansal SS. Kichler A. Mason AJ. ChemBioChem. 2010; 11: 1266
  • 16 Stubbs M. McSheehy PM. Griffiths JR. Bashford CL. Mol. Med. Today 2000; 6: 15
  • 17 Weerakkody D. Moshnikova A. Thakur MS. Moshnikova V. Daniels J. Engelman DM. Andreev OA. Reshetnyak YK. Proc. Natl. Acad. Sci., U.S.A. 2013; 110: 5834