Section of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO), University of Geneva, Switzerland.
Tissue Barriers. 2023 Jan 2;11(1):2060692. doi: 10.1080/21688370.2022.2060692. Epub 2022 Apr 3.
The pentapeptide L-R5 has previously been shown to transiently increase the permeability of nasal epithelial cell layers , allowing paracellular transport of molecules of up to 4 kDa. Protein kinase C zeta (PKC ζ), a member of a family of serine/threonine kinases was shown to be involved in tight junction modulation induced by L-R5. We show here that the ability of L-R5 to modulate tight junctions is comparable to other permeability enhancers such as bilobalide, latrunculin A or C. Interaction of the peptide with the target protein occurs via electrostatic interaction, with the presence of positive charges being essential for its functionality. L-R5 is myristoylated to allow quick cell entry and onset of activity. While no epithelial cytotoxicity was detected, the hydrophobic myristoyl rest was shown to cause haemolysis. Taken together, these data show that a structural optimization of L-R5 may be possible, both from a toxicological and an efficacy point of view.
先前的研究表明，五肽 L-R5 可短暂增加鼻上皮细胞层的通透性，允许分子量高达 4 kDa 的分子经细胞旁途径转运。蛋白激酶 C ζ（PKC ζ）是丝氨酸/苏氨酸激酶家族的成员，它参与了 L-R5 诱导的紧密连接调节。我们在这里表明，L-R5 调节紧密连接的能力可与其他通透性增强剂（如银杏内酯、Latrunculin A 或 C）相媲美。该肽与靶蛋白的相互作用通过静电相互作用发生，正电荷的存在对于其功能至关重要。L-R5 被豆蔻酰化以允许快速进入细胞并开始发挥作用。虽然没有检测到上皮细胞毒性，但疏水性豆蔻酰基部分被证明会引起溶血。总之，这些数据表明，从毒理学和疗效的角度来看，L-R5 的结构优化可能是可行的。
