Solyev Pavel N, Isakova Elena B, Olsufyeva Evgenia N
Engelhardt Institute of Molecular Biology, 32 Vavilov St., 119991 Moscow, Russia.
Gause Institute of New Antibiotics, 11 Bolshaya Pirogovskaya St., 119021 Moscow, Russia.
Antibiotics (Basel). 2023 May 11;12(5):894. doi: 10.3390/antibiotics12050894.
A significant increase of microbial resistance to glycopeptides (especially vancomycin-resistant enterococci and ) prompted researchers to design new semisynthetic glycopeptide derivatives, such as dual-action antibiotics that contain a glycopeptide molecule and an antibacterial agent of a different class. We synthesized novel dimeric conjugates of kanamycin A with glycopeptide antibiotics, vancomycin and eremomycin. Using tandem mass spectrometry fragmentation, UV, IR, and NMR spectral data, it was unequivocally proven that the glycopeptide is attached to the kanamycin A molecule at the position 1 of 2-deoxy-D-streptamine. New MS fragmentation patterns for -Cbz-protected aminoglycosides were discovered. It was found that the resulting conjugates are active against Gram-positive bacteria, and some are active against vancomycin-resistant strains. Conjugates of two different classes can serve as dual-target antimicrobial candidates for further investigation and improvement.
微生物对糖肽类（尤其是耐万古霉素肠球菌）的耐药性显著增加，促使研究人员设计新的半合成糖肽衍生物，例如含有糖肽分子和另一类抗菌剂的双效抗生素。我们合成了卡那霉素A与糖肽抗生素万古霉素和埃瑞霉素的新型二聚体缀合物。利用串联质谱裂解、紫外、红外和核磁共振光谱数据，明确证明糖肽在2-脱氧-D-链霉胺的1位连接到卡那霉素A分子上。发现了-Cbz保护的氨基糖苷类新的质谱裂解模式。结果表明，所得缀合物对革兰氏阳性菌有活性，有些对耐万古霉素菌株也有活性。两类不同的缀合物可作为双靶点抗菌候选物用于进一步研究和改进。
