Synthesis of Novel Fatty-Acyl Gratisin Derivatives

Autor:	Kenta Fujinuma, Takuji Harada, Yoshiki Uchida, Makoto Tamaki, Masahiro Kimura, Kazumasa Takanashi, Mitsuno Shindo
Rok vydání:	2012
Předmět:	Dose-Response Relationship Drug Molecular Structure Chemistry Stereochemistry Ionic bonding Microbial Sensitivity Tests General Chemistry General Medicine Antimicrobial Hemolysis Peptides Cyclic Dissociation (chemistry) Anti-Bacterial Agents Membrane Microbial resistance Drug Discovery
Zdroj:	Chemical and Pharmaceutical Bulletin. 60:743-746
ISSN:	1347-5223 0009-2363
DOI:	10.1248/cpb.60.743
Popis:	To find candidates with high antimicrobial and low hemolytic activities, many gratisin (GR) analogues have been designed and synthesized. In the present account, we synthesized novel derivatives of GR having both the polycationic and fatty acyl groups, cyclo{-Val(1)-Orn(2)-Leu(3)-D-Phe(4)-Pro(5)-D-Lys(6)(X)-Val(7)-Orn(8)-Leu(9)-D-Phe(10)-Pro(11)-D-Lys(12)-} {X=-CO(CH(2))(6)CH(3) (1), -Lys-CO(CH(2))(6)CH(3) (2), -(Lys)(2)-CO(CH(2))(6)CH(3) (3), and -(Lys)(3)-CO(CH(2))(6)CH(3) (4)}, and examined the biological activities. Among them, we found that 2-4 have differential ionic interaction against the prokaryotic membrane and eukaryotic membrane. In other words, the dissociation with high antimicrobial activity and low hemolytic activity is caused by the addition of D-Lys(6)-{(Lys)(n)-CO(CH(2))(6)CH(3)} residues at position 6 of [D-Lys(6,12)]-GR. Our findings should be helpful in finding drug candidates with high antimicrobial activity and low hemolytic activity that are capable of combating microbial resistance.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25e4912a266d57c88dfbe243b56ad713 https://doi.org/10.1248/cpb.60.743 Zobrazit plný text záznamu