Small cyclic agonists of iron regulatory hormone hepcidin.
Small cyclic agonists of iron regulatory hormone hepcidin.
复制标题
DOI：
10.1016/j.bmcl.2015.03.012
复制
发表时间：
2015-11-01
影响因子：
2.7
通讯作者：
Ruchala P
中科院分区：
文献类型：
--
作者：
Chua K;Fung E;Micewicz ED;Ganz T;Nemeth E;Ruchala P
小分子海普西丁是铁调节激素海普西丁的体外和体内活性模拟物。它们含有各种不寻常的氨基酸，包括：N-取代、β-HO-和D-氨基酸，它们的结合取决于特定的MINHEPIDIN。在目前的研究中，我们试图通过肽环化来限制不寻常的/更昂贵的氨基酸衍生物的使用。合成了一种新型的环状海普西丁模拟物，并对其进行了体外活性测试，在低纳摩尔浓度下表现出良好的活性。尽管如此，最活跃的环状化合物(MHS17)的活性大约比亲本的MINHIVIDIN PR73低十倍。总而言之，我们的研究结果表明，环化是合成海普西丁模拟物的可行方法。
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 cyclisation. 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 cyclisation is viable approach in the synthesis of hepcidin mimetics.