Division of Organic Chemistry CSIR-National Chemical Laboratory (NCL), Dr. Homi Bhabha Road, Pune 411008, India.
Institute for Advanced Study, Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
Bioorg Med Chem Lett. 2020 Apr 15;30(8):127039. doi: 10.1016/j.bmcl.2020.127039. Epub 2020 Feb 17.
In this letter, we report a series of five new RGD-containing cyclic peptides as potent inhibitors to αvβ integrin protein. We have incorporated various unnatural lipophilic amino acids into the cyclic RGD framework of cilengitide, which is selective for αvβ integrin. All the newly synthesized cyclic peptides were evaluated in vitrosolid phase binding assay and investigated for their bindingbehaviourtowards integrin subtypes. All the cyclic peptides were synthesized in excellent yield following solution-phase coupling strategy. The cyclic RGD peptides 1a-e exhibited IC of 9.9, 5.5, 72, 11 and 3.3 nM, respectively, towardsαvβ integrin protein. This finding offers further opportunities for the introduction unusual amino acids into the cyclic peptide framework of cilengitide.
在这封信中，我们报告了一系列五个新的含 RGD 的环肽作为有效的 αvβ 整联蛋白抑制剂。我们已经将各种非天然疏水性氨基酸整合到西仑肽的环 RGD 骨架中，西仑肽对 αvβ 整联蛋白具有选择性。所有新合成的环肽都在体外固相结合测定法中进行了评估，并研究了它们与整合素亚型的结合行为。所有的环肽都是按照溶液相偶联策略以优异的产率合成的。环 RGD 肽 1a-e 对αvβ 整联蛋白蛋白的 IC 分别为 9.9、5.5、72、11 和 3.3 nM。这一发现为将不寻常的氨基酸引入西仑肽的环肽骨架提供了进一步的机会。
