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An antifungal peptide targeting P4-ATPase function is synthesized based on Cdc50 loop region to identify peptides sensitize caspofungin by blocking flippase function. It was found that myristylated peptides based on “AS 15 sequence” was effective at high concentrations. A modified peptide,“AW9-Ma” showed minimum inhibitory concentration (MIC) of 64 pg/mL against H99 wild type and fractional inhibitory concentration (FIC) index value of 0.5 when used with caspofungin. With the AW9-Ma peptide, C. neoformans wild type was highly sensitive to caspofungin with a MIC of 4 pg/mL, the same as cdc50A mutant. Further assays with flow cytometry showed inhibition of lipid flippase enzyme activity and significant accumulation of phosphatidylserine on the cell surface. It was confirmed that the peptide co-localized with mCherry-tagged P4-ATPase protein Apt 1 in C. neoformans. Modification studies of AW9 sequence …