Novel gratisin derivatives with high antimicrobial activity and low hemolytic activity

作者：Tamaki Makoto^*; Imazeki Yukie; Shirane Aya; Fujinuma Kenta; Shindo Mitsuno; Kimura Masahiro; Uchida Yoshiki

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(1): 440-443.

DOI：10.1016/j.bmcl.2010.10.122

• Gratisin analogues
• Synthesis
• High antimicrobial activity
• Low hemolytic activity
• Structure-activity relationship

The substitution of each constituent amino acid residue of gratisin (GR) with Ala residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic and hemolytic activities of GR. Among them, the substitution of Pro residues at positions 5 and 5' with a cationic amino acid residues (Lys and Arg) results the high antibiotic activity and the low toxicity against human lood cells. Thus, we have found a novel position on the scaffold of GR at Pro5,5' residues whose modification will significantly lower the unwanted hemolytic activity and enhance the desired antibiotic activity.

• 出版日期2011-1