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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Isolation and Structure Elucidation of Thiazomycin -A Potent Thiazolyl Peptide Antibiotic from Amycolatopsis fastidiosa
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Isolation and Structure Elucidation of Thiazomycin -A Potent Thiazolyl Peptide Antibiotic from Amycolatopsis fastidiosa

机译:噻唑霉素-一种强力的支链淀粉病性噻唑基肽抗生素的分离和结构鉴定

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Thiazolyl peptides are a class of rigid macrocyclic compounds richly populated with thiazole rings.They are highly potent antibiotics but none have been advanced to clinic due to poor aqueous solubility.Recent progress in this field prompted a reinvestigation leading to the isolation of a new thiazolyl peptide,thiazomycin,a congener of nocathiacins.Thiazomycin possesses an oxazolidine ring as part of the amino-sugar moiety in contrast to the dimethyl amino group present in nocathiacin I.The presence of the oxazolidine ring provides additional opportunities for chemical modifications that are not possible with other nocathiacins.Thiazomycin is extremely potent against Gram-positive bacteria both in vitro and in vivo.The titer of thiazomycin in the fermentation broth was very low compared to the nocathiacins I and III.The lower titer together with its sandwiched order of elution presented significant challenges in large scale purification of thiazomycin.This problem was resolved by the development of an innovative preferential protonation based one-and/or two-step chromatographic method,which was used for pilot plant scale purifications of thiazomycin.The isolation and structure elucidation of thiazomycin is herein described.
机译:噻唑基肽是一类富含噻唑环的刚性大环化合物,是强效抗生素,但由于水溶性差而尚未被推向临床,该领域的最新进展促使人们进行了重新研究,从而分离出一种新的噻唑基肽与Nocathiacin I中存在的二甲基氨基相反,Thiazomycin拥有一个恶唑烷环作为氨基糖部分的一部分。噻唑烷环的存在为恶唑烷环的化学修饰提供了更多的机会噻唑霉素在体外和体内均对革兰氏阳性细菌具有极强的效力,与肉毒杆菌素I和III相比,发酵液中的噻唑霉素的滴度非常低。较低的滴度及其夹心的洗脱顺序显示出显着性噻唑霉素的大规模纯化面临挑战。发明一种基于优先质子化的创新型一步和/或两步色谱方法,该方法用于噻唑霉素的中试规模工厂纯化。本文描述了噻唑霉素的分离和结构鉴定。

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