Multimeric glycotherapeutics: New paradigm
Multimeric glycotherapeutics: New paradigm
复制标题
多聚糖疗法：新范例
作者：
N. Bovin;A. Tuzikov;A. Chinarev;A. Gambaryan
抗粘附治疗的一般原理是在可溶性受体类似物的帮助下抑制微生物粘附到宿主细胞。尽管这一概念具有明显的吸引力，而且存在已久，但“后抗生素时代”的治疗方法尚未出现。这可以通过抗粘附药物要求的矛盾性来解释：为了有效，药物必须是多价的，即大分子，但为了获得FDA批准，它应该是小分子。克服这种矛盾的一种方法是糖肽的自组装。糖肽的碳水化合物部分负责与微生物的凝集素结合，而简单的肽部分负责与所谓的tectomers结合。根据结构的不同，构造体可以自发形成，也可以在微生物的促进下形成。特别地，已经获得了仅在流感病毒存在下才能转化为结构体的唾液酸肽。因此，抗粘附治疗的新策略可以制定如下：（1）鉴定特定病毒（细菌）的寡糖受体;（2）优化肽部分;（3）常规试验。该策略的预期优点如下：（i）无聚合物;（ii）病毒体完全被结构体覆盖，即封闭是完全和不可逆的;（iii）快速和合理的先导物鉴定和优化;（iv）最小的副作用;（V）微生物对天然受体的抗性的潜力低于模拟物的情况。2004年出版。
The general principle of anti-adhesion therapy is the inhibition of microorganism adhesion to the host cell with the help of a soluble receptor analog. Despite an evident attractiveness of the concept and its long existence, the therapeutics of the ‘post-antibiotic era’ have not yet appeared. This can be explained by the contradictoriness of requirements for anti-adhesion drugs: to be efficient a drug must be multivalent, i.e. large molecule, but to obtain FDA approval it should be a small molecule. A way to overcome this contradiction is self-assembly of glycopeptides. The carbohydrate part of glycopeptide is responsible for binding with the lectin of microorganisms, whereas a simple peptide part is responsible for an association to the so-called tectomers. Depending on the structure, tectomers are formed either spontaneously or upon promotion of a microorganism. In particular, sialopeptide, which is capable of converting to a tectomer only in the presence of the influenza virus, has been obtained. Thus, the new strategy of anti-adhesion therapy can be formulated as follows: (1) identification of oligosaccharide-receptor for a particular virus (bacteria); (2) optimization of the peptide part; (3) conventional trials. The expected advantages of this strategy are the following: (i) no polymer; (ii) a virion completely covered with a tectomer, i.e. blocking is both complete and irreversible; (iii) rapid and rational lead identification and optimization; (iv) minimum side effects; (v) potential for microorganism resistance to natural receptor is lower than in the case of mimetics. Published in 2004.
IgG3 抗链球菌 A 组碳水化合物 (GAC) 抗体与链球菌 A 组疫苗的相互作用：增强和抑制抗 GAC、抗同种型和抗独特型抗体的作用。
DOI：
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发表时间：
1987
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Greenspan,NS;Monafo,WJ;Davie,JM
通讯作者：
Davie,JM
影响因子：
3.7
作者：
Matrosovich, MN;Krauss, S;Webster, RG
通讯作者：
Webster, RG
影响因子：
5.6
作者：
CHOU, KC;POTTLE, M;SCHERAGA, HA
通讯作者：
SCHERAGA, HA