Small cyclic agonists of iron regulatory hormone hepcidin

Bioorg Med Chem Lett. 2015 Nov 1;25(21):4961-4969. doi: 10.1016/j.bmcl.2015.03.012. Epub 2015 Mar 12.

Abstract

Minihepcidins are in vitro and in vivo active mimetics of iron-regulatory hormone hepcidin. They contain various unusual amino acids including: N-substituted, β-homo-, and d-amino acids with their combination depending on particular minihepcidin. In the current study, we sought to limit the use of unusual/more expensive amino acids derivatives by peptide cyclization. Novel cyclic mimetics of hepcidin were synthesized and tested in vitro and showed activity at low nanomolar concentration. Nonetheless, the most active cyclic compound (mHS17) is approximately ten times less active than the parental minihepcidin PR73. Collectively, our findings suggest that cyclization is viable approach in the synthesis of hepcidin mimetics.

Keywords: Cyclization; Iron; Minihepcidins; Peptides; S-alkylation of peptides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Hepcidins / agonists*
  • Humans
  • Molecular Structure
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Hepcidins
  • Peptides