Peptides with indirect in vivo activity against an intracellular pathogen: selective lysis of infected macrophages.
Peptides with indirect in vivo activity against an intracellular pathogen: selective lysis of infected macrophages.
复制标题
对细胞内病原体具有间接体内活性的肽：选择性裂解受感染的巨噬细胞。
DOI：
10.1046/j.1397-002x.2001.10995.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Elzer,PhilipH
中科院分区：
文献类型：
--
作者：
Yokum,TS;Hammer,RP;McLaughlin,MarkL;Elzer,PhilipH
A collection of natural peptides, simplified analogs of natural peptides,de novoamphipathic peptides andde novoamphipathic peptides composed of 50–80% α,α‐dialkylated glycines (α,α‐Dags) were synthesized on solid‐phase resin as the C‐terminus amides usingN‐α‐fluorenylmethyloxycarbonyl protection. The synthesis of the peptides rich in α,α‐Dags used acid fluoride coupling methods. The peptides show antimicrobial activity againstEscherichia coliandStaphylococcus aureusbut no direct antimicrobial activity againstBrucella abortusat 100 µmin vitro. However,in vivotreatment with several of these peptides results in significant reductions ofB. abortusin chronically infected immune BALB/c mice relative to infected control animals. The chronically infected mice were susceptible to peptide toxicity at much lower peptide doses than control animals. The highest nonlethal dose for infected mice was only 25 µg for melittin, whereas 500 µg doses were nonlethal for many of the other peptides. Several of the α,α‐Dag‐rich peptides selectively destroyB. abortus‐infected murine macrophagesin vitro. Thus, these peptides apparently reduce the bacterial loadin vivoby destroying a portion of the infected macrophages and exposing the sequestered bacteria to the immune response in the mice.
