Small cyclic agonists of iron regulatory hormone hepcidin

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Chua, Kristine¹  Fung, Eileen¹  Micewicz, Ewa D.²  Ganz, Tomas¹  Nemeth, Elizabeta¹  Ruchala, Piotr^3,4 

[1] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Pasarow Mass Spectrometry Lab, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA

关键词: Minihepcidins;    Peptides;    S-alkylation of peptides;    Iron;    Cyclization;   

DOI  :  10.1016/j.bmcl.2015.03.012

来源: Elsevier

【 摘 要 】

Minihepcidins are in vitro and in vivo active mimetics of iron-regulatory hormone hepcidin. They contain various unusual amino acids including: N-substituted, beta-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. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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