Bivalent HIV-1 fusion inhibitors based on peptidomimetics
Bivalent HIV-1 fusion inhibitors based on peptidomimetics
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DOI：
10.1016/j.bmc.2020.115812
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发表时间：
2020-12-15
影响因子：
3.5
通讯作者：
Tamamura, Hirokazu
中科院分区：
文献类型：
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作者：
Kobayakawa, Takuya;Ebihara, Kento;Tamamura, Hirokazu
膜融合是抑制HIV-1复制的有效靶点。HIV-1包膜蛋白gp 41中含有的34-mer片段肽（C34）具有显著的抗HIV活性。先前，发现通过在其C-末端的二硫桥连接的C34的二聚衍生物比C34肽单体具有更有效的抗HIV活性。迄今为止，已经报道了几种拟肽小抑制剂，但大多数具有比与C34相关的肽衍生物更低的效力。在本研究中，我们将这种二聚化的概念应用于这些拟肽小抑制剂，并设计了几个二价拟肽HIV-1融合抑制剂。证明了交联两种拟肽化合物的接头长度的重要性，并产生了几种含有栓系拟肽的有效二价抑制剂。
Membrane fusion is a valid target for inhibition of HIV-1 replication. A 34-mer fragment peptide (C34), which is contained in the HIV-1 envelope protein gp41, has significant anti-HIV activity. Previously, a dimeric derivative of C34 linked by a disulfide bridge at its C-terminus was found to have more potent anti-HIV activity than the C34 peptide monomer. To date, several peptidomimetic small inhibitors have been reported, but most have lower potency than peptide derivatives related to C34. In the present study we applied this dimerization concept to these peptidomimetic small inhibitors and designed several bivalent peptidomimetic HIV-1 fusion inhibitors. The importance of the length of linkers crosslinking two peptidomimetic compounds was demonstrated and several potent bivalent inhibitors containing tethered peptidomimetics were produced.