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[摘要]：In the present study, novel eight GS derivatives having the octanoyl-(Lys)(n)-moieties, cyclo{-Val-Orn-Leu-D-Phe-Pro(4 beta-NH-X)-Val-Orn-Leu-D-Phe-Pro-} {X = -H (1), and -(Lys)(n)-CO(CH(2))(6)CH(3) n = 0 (2), 1 (3), 2 (4), and 3 (5)} and cyclo{-Val-Orn-Leu-D-Phe-Pro(4 alpha-NH-X)-Val-Orn-Leu-D-Phe-Pro-} {X = -H (6), and (Lys)(n)-CO(CH(2))(6)CH(3) n = 1 (7), and 2 (8)} were synthesized. Among them, 4, 5 and 8 result the high antibiotic activity against both Gram-positive and Gram-negative microorganisms tested. In addition, 4 and 5 showed very low hemolytic activity compared with that of GS. Thus, the introduction of the excess amino groups and the fatty acyl moiety to the gamma-NH(2) group of Pro(5) residue in GS molecule lowered the unwanted hemolytic activity and enhanced the desired antibiotic activity. (C) 2011 Elsevier Ltd. All rights reserved. |
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