Antimicrobial α,α-Dialkylated Amino Acid Rich Peptides with in-Vivo Activity against an Intracellular Pathogen
Antimicrobial α,α-Dialkylated Amino Acid Rich Peptides with in-Vivo Activity against an Intracellular Pathogen
复制标题
具有抗细胞内病原体体内活性的抗菌 α,α-二烷基化氨基酸丰富肽
DOI：
10.1021/jm960451n
复制
发表时间：
1996
影响因子：
7.3
通讯作者：
McLaughlin Ml
中科院分区：
文献类型：
--
作者：
T. Yokum;P. Elzer;McLaughlin Ml
The development of antibiotic resistance is threatening a return to the preantibiotic era. 1 This threat is hastened by the reliance on only a handful of distinct mechanisms of action among the vast majority of the commercially available drugs. 2 This problem alone is sufficient to warrant development of novel antimicrobial agents with unique modes of action. 3 In addition, new methods of controlling intracellular pathogens are needed because conventional antibiotic therapy and the host’s immune response are not very effective against sequestered microorganisms. 4 Brucella abortus is an intracellular pathogen which lives and replicates in macrophages and quickly establishes chronic experimental infections in mice. 5 Herein, we report the invitro antibacterial and in-vivo anti-brucellae activity of a series of peptides (1-10).Peptides 2-10 are composed of 50-80% R, R-dialkylated amino acids. The design of these peptides is loosely based on the natural antimicrobial peptides peptaibols. 6-8 Peptaibols have several R-aminoisobutyric acid (Aib) residues, are acetylated on the N-terminus, and have an amino alcohol at the C-terminus. 7 De-novo peptides that include only a putative amphipathic helix have activity comparable to or greater than that of native antimicrobial peptides. 10 Amphipathic peptides with g18 residues can have very high cytotoxicity, 11 but simply shortening the peptides to 14 residues reduces cytotoxicity and retains much of the antimicrobial
