Improved solid-phase synthesis of alpha,alpha-dialkylated amino acid-rich peptides with antimicrobial activity.
Improved solid-phase synthesis of alpha,alpha-dialkylated amino acid-rich peptides with antimicrobial activity.
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改进具有抗菌活性的富含 α,α-二烷基化氨基酸的肽的固相合成。
DOI：
10.1111/j.1399-3011.2005.00312.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Hammer,RP
中科院分区：
文献类型：
--
作者：
Haynes,SR;Hagins,SD;Juban,MM;Elzer,PH;Hammer,RP
A homologous series of nonapeptides and their acetylated versions were successfully prepared using solid‐phase synthetic techniques. Each nonapeptide was rich in α,α‐dialkylated amino acids [one 4‐aminopiperidine‐4‐carboxylic acid (Api) and six α‐aminoisobutyric acid (Aib) residues] and also included lysines or lysine analogs (two residues). The incorporation of the protected dipeptide 9‐fluorenylmethyloxycarbonyl (Fmoc)‐Aib‐Aib‐OH improved the purity and overall yields of these de novo designed peptides. The helix preference of each nonapeptide was investigated in six different solvent environments, and each peptide's antimicrobial activity and cytotoxicity were studied. The 310‐helical, amphipathic design of these peptides was born out most prominently in the N‐terminally acetylated peptides. Most of the peptides exhibited modest activity againstEscherichia coliand no activity againstStaphylococcus aureus. The nonacetylated peptides (concentrations ≤100μm) and the acetylated peptides (concentrations ≤200μm) did not exhibit any significant cytotoxicity with normal (nonactivated) murine macrophages.
