Aggregation and Its Influence on the Immunomodulatory Activity of Synthetic Innate Defense Regulator Peptides

作者：Haney Evan F; Wu Bing; Lee Kelsey; Hilchie Ashley L; Hancock Robert E W

来源：Cell Chemical Biology, 2017, 24(8): 969-+.

DOI：10.1016/j.chembiol.2017.07.010

There is increasing interest in developing cationic host defense peptides (HDPs) and their synthetic derivatives as antimicrobial, immunomodulatory, and anti-biofilm agents. These activities are often evaluated without considering biologically relevant concentrations of salts or serum; furthermore certain HDPs have been shown to aggregate in vitro. Here we examined the effect of aggregation on the immunomodulatory activity of a synthetic innate defense regulator peptide, 1018 (VRLIVAVRIWRR-NH2). A variety of salts and solutes were screened to determine their influence on 1018 aggregation, revealing that this peptide "salts out'' of solution in an anion-specific and concentration-dependent manner. Furthermore, the immunomodulatory activity of 1018 was found to be inhibited under aggregation-promoting conditions. A series of 1018 derivatives were synthesized with the goal of disrupting this self-assembly process. Indeed, some derivatives exhibited reduced aggregation while maintaining certain immunomodulatory functions, demonstrating that it is possible to engineer optimized synthetic HDPs to avoid unwanted peptide aggregation.

• 出版日期2017-8-17