Design And Synthesis Of Series Of Pseudocyclopeptides Based On Loloatin C And Preliminary Study On Their Antibacterial Mechanism

Loloatin C was discovered and separated from tropical ocean bacterial laboratory, which is a cyclodecapeptide compound. Many experiments have shown that Loloatin C has remarkable activity to G+ and G- bacteria. Three cyclohexapeptides (named north, middle, and south cyclohexapeptide) narrowed down from Loloatin C by sliding window were figured out and synthesized. Antimicrobial screening conformed that the pharmacophore of Loloatin C contains structure of–D-Tyr-Pro-Trp-D-Phe-. Based on these results, we design and synthesize series of pseudocyclicpeptides, which contain–D-Tyr-Pro-Trp-D-Phe-, expecting to get more active compounds.In order to study the antibacterial mechanism of Loloatin C, growth inhibition of loloatin C to E. coli was investigated under the existence or without the existence of CCCP. The activity ofβ-galactose glycosidase when Loloatin C interacted with E. coli was also studied by using lactose as substrate.The following results have been obtained: (1) Five linear precursor peptides (S1-1, S1-2, S, S2-1, S2-2)were synthesized and the overall yields were about 40%; three pseudo cyclopeptides (C1-2, C2-1, C2-2) were obtained but the overall yield were low, only 2%; (2) More E.coli bacteria survive under the existence of CCCP, which we can infer that the problem of resistance won't happen due to the excessive expression of efflux system of bacteria. Besides, as the concentration of Loloatin C increases, the activity ofβ-galactose glycoside from E.coli gets stronger.