Histidine-rich Modification of a Scorpion-derived Peptide Improves Bioavailability and Inhibitory Activity against HSV-1

Zeng, Zhengyang; Zhang, Runhong; Hong, Wei; Cheng, Yuting; Wang, Huijuan; Lang, Yange; Ji, Zhenglin; Wu, Yingliang; Li, Wenxin; Xie, Youli; Cao, Zhijian

It has been reported that an artificial modified histidine-rich amphipathic peptide LAH4 exhibits efficient DNA delivery into mammalian cells [22] . The presence of histidine residues and a well-defined hydrophobic face have been identified as determinants of peptide delivery efficiency. The modification of a scorpion-derived anti-HCV peptide Ctry2459 into histidine-rich derivative peptides also significantly enhanced bioavailability and anti-HCV activity [16] . Referring to the design strategy of LAH4 and Ctry2459, several histidine residues were added in the derivative peptides, which were named Eval418-FH2 (Figure 5b ), Eval418-FH3 (Figure 5c ), Eval418-FH4 (Figure 5d ) and Eval418-FH5 (Figure 5e ). The secondary structures of the derivative peptides were predicted and determined using Swiss PDB Viewer software and circular dichroism (CD) spectroscopy (Figure 5b-e) , respectively. The addition of histidine residues did not disrupt the pattern and stabilization of secondary structures, and the amphiphilicity was enhanced. The sequence alignments of Eval418 and its derivative peptides are shown in Figure 5f .