Ciabatti R, Malabarba A
Biosearch Italia Spa, Gerenzano (VA), Italy.
Farmaco. 1997 May;52(5):313-21.
Glycopeptides are a class of naturally occurring antibiotics produced by fermentation of microorganisms. They inhibit cell wall biosynthesis in bacteria by forming a complex with the C-terminal D-alanyl-D-alanine of growing peptidoglycan chains. Glycopeptides are active against Gram-positive bacteria including the major pathogens. Among all the glycopeptides that have been discovered, only vancomycin and teicoplanin are on the market for the clinical use. By modification of the natural glycopeptide it is possible to increase its activity against methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci. Basic amides of teicoplanin aglycon have produced one compound endowed with interesting activity against Gram-negative bacteria because of its ability to cross the outer membrane of this last bacteria. Selective degradation of teicoplanin has given a tetrapeptide, a key intermediate that has been used as starting material for the synthesis of new non natural glycopeptides. One of them has shown a weak but promising activity against Van A Enterococci highly resistant to natural glycopeptides.
糖肽类是一类通过微生物发酵产生的天然抗生素。它们通过与正在生长的肽聚糖链的C末端D-丙氨酰-D-丙氨酸形成复合物来抑制细菌细胞壁的生物合成。糖肽类对包括主要病原体在内的革兰氏阳性菌具有活性。在已发现的所有糖肽类中，只有万古霉素和替考拉宁在临床上用于治疗。通过对天然糖肽进行修饰，可以提高其对耐甲氧西林金黄色葡萄球菌和凝固酶阴性葡萄球菌的活性。替考拉宁苷元的碱性酰胺产生了一种化合物，该化合物对革兰氏阴性菌具有有趣的活性，因为它能够穿过这种细菌的外膜。替考拉宁的选择性降解产生了一种四肽，这是一种关键中间体，已被用作合成新的非天然糖肽的起始原料。其中一种对天然糖肽高度耐药的Van A肠球菌显示出微弱但有前景的活性。
