...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Antibiotics: An International Journal >Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of beta-lactams
【24h】

Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of beta-lactams

机译：改性牙霉素，具有降低的真核毒性，可增强β-内酰胺的抗菌活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Tunicamycins (TUN) are inhibitors of the UDP-HexNAc: polyprenol-P HexNAc-1-P transferase family of enzymes, which initiate the biosynthesis of bacterial peptidoglycan and catalyze the first step in eukaryotic protein N-glycosylation. The TUN are therefore general and potent toxins to both eukaryotes and prokaryotes. Screening a library of synthetic TUN against Bacillus and yeast identified TUN that are antibacterial, but have significantly reduced eukaryotic toxicity. One of these (Tun-15: 0) differs from the native TUN control only by the lack of the conjugated double bond in the tunicaminyl N-acyl group. Tun-15: 0 also showed reduced inhibition for protein N-glycosylation in a Pichia-based bioassay. Natural TUN was subsequently modified by chemically reducing the N-acyl double bond (TunR1) or both the N-acyl and uridyl double bonds (TunR2). TunR1 and TunR2 retain their antibacterial activity, but with considerably reduced eukaryotic toxicity. In protein N-glycosylation bioassays, TunR1 is a less potent inhibitor than native TUN and TunR2 is entirely inactive. Importantly, the less toxic TunR1 and TunR2 both enhance the antibacterial activity of beta-lactams: oxacillin by 32- to 64-fold, comparable with native TUN, and with similar enhancements for methicillin and penicillin G. Hence, the modified TUNs, TunR1 and TunR2, are potentially important as less-toxic synergistic enhancers of the beta-lactams.
机译：Tunicamycins（TUN）是UDP-HexNAC的抑制剂：聚丙烯-P六己-1-P转移酶酶系列，其引发细菌肽聚糖的生物合成，并催化真核蛋白N-糖基化的第一步。因此，TUN是一般和有效的毒素到真核生物和原核生物。筛选杆菌和酵母鉴定的杆菌和酵母鉴定的抗菌性，但显着降低了真核毒性。其中一个（TUN-15：0）仅通过缺少羟氰基N-酰基中的缀合的双键来不同于天然枪控制。 TUN-15：0还表明，在基于PICHIA的生物测定中，对蛋白质N-糖基化的抑制性降低。随后通过化学减小N-酰基双键（TUNR1）或N-酰基和尿苷二次键（TUNR2）来改变天然曲调。 TUNR1和TUNR2保留其抗菌活性，但显着降低了真核毒性。在蛋白质N-糖基化生物测定中，TUNR1是比天然支架的抑制剂较少，并且TUNR2完全无活性。重要的是，有毒的屯r1和螺旋曲线2较低，均增强β-内酰胺的抗菌活性：牛奶蛋白的抗菌活性32-至64倍，与天然锡相当，并且具有类似的甲氧西林和青霉素G的增强。因此，改进的隧道，隧道和TUNR2可能是β-内酰胺的少于有毒协同增强剂。

著录项

  • 来源
  • 作者

    Price Neil P. J.; Hartman Trina M.; Li Jiakun; Velpula Kiran K.; Naumann Todd A.; Guda Maheedhara R.; Yu Biao; Bischoff Kenneth M.;

  • 作者单位

    ARS USDA Natl Ctr Agr Utilizat Res 1815 North Univ St Peoria IL 61604 USA;

    ARS USDA Natl Ctr Agr Utilizat Res 1815 North Univ St Peoria IL 61604 USA;

    Chinese Acad Sci Shanghai Inst Organ Chem State Key Lab Bioorgan &

    Nat Prod Chem Shanghai;

    Univ Illinois Coll Med Peoria Dept Canc Biol &

    Pharmacol Peoria IL USA;

    ARS USDA Natl Ctr Agr Utilizat Res 1815 North Univ St Peoria IL 61604 USA;

    Univ Illinois Coll Med Peoria Dept Canc Biol &

    Pharmacol Peoria IL USA;

    Chinese Acad Sci Shanghai Inst Organ Chem State Key Lab Bioorgan &

    Nat Prod Chem Shanghai;

    ARS USDA Natl Ctr Agr Utilizat Res 1815 North Univ St Peoria IL 61604 USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号