Inhibition of Melittin Activity Using a Small Molecule with an Indole Ring
Inhibition of Melittin Activity Using a Small Molecule with an Indole Ring
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DOI：
10.1021/acs.jpcb.2c03595
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发表时间：
2022-08-01
影响因子：
3.3
通讯作者：
Maruyama, Tatsuo
中科院分区：
文献类型：
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作者：
Kanemitsu, Sayuki;Morita, Kenta;Maruyama, Tatsuo
我们研究了 D-氨基酸作为针对 L-肽毒素的潜在抑制剂。在测试的 L- 和 D- 氨基酸中，我们发现 D-色氨酸 (D-Trp) 可以作为蜂毒肽诱导的溶血的抑制剂。然后我们评估了各种色氨酸衍生物，发现5-氯色胺（5CT）对蜂毒肽的抑制作用最大。抑制剂的吲哚环、氨基和空间位阻在蜂毒肽活性的抑制中发挥重要作用。尽管5CT尺寸小、分子结构简单，但其IC50约为13μg/mL。荧光猝灭、圆二色性测量和尺寸排阻色谱显示 5CT 与蜂毒肽中的 Trp19 相互作用并影响其形成
We investigated D-amino acids as potential inhibitors targeting L-peptide toxins. Among the L- and D-amino acids tested, we found that D-tryptophan (D-Trp) acted as an inhibitor of melittin-induced hemolysis. We then evaluated various Trp derivatives and found that 5-chlorotryptamine (5CT) had the largest inhibitory effect on melittin. The indole ring, amino group, and steric hindrance of an inhibitor played important roles in the inhibition of melittin activity. Despite the small size and simple molecular structure of 5CT, its IC50 was approximately 13 mu g/mL. Fluorescence quenching, circular dichroism measurements, and size-exclusion chromatography revealed that 5CT interacted with Trp19 in melittin and affected the formation