"一珠一化合物"组合化学方法筛选抗万古霉素耐药菌活性化合物

目的 寻找新的抗万古霉素耐药菌活性化合物。方法 首次采用固相法合成了分别用生物素（Biotin）和^125I标记的D－Ala-D-Lactate和D－Ala-D-Ala探针化合物以及18个结构限定性的多肽和多肽衍生物化学库,并建立了“一珠一化合物”组合正交筛选实验方法。结果 发现了一个新的体外抑制低水平万古霉素耐药菌的化合物（Enterococcus faecalis,ATCC 51299,MIC值为17.5mg/L）。该化合物对万古霉素敏感菌菌株的抑制活性为MIC6.25mg/L(Staphylococcus aurreus,ATCC 25923）。结论 “一珠一化合物”组合正交筛选方法可以用于研究小分子间的相互作用。

Identification of the anti-vancomycin-resistance peptides from "one-bead,one-compound" libraries

Aim To discover new active compounds against the vancomycin resistant.Methods Designed and solid phase synthesized Biotin and 125 I labeled D Ala D Lactate and D Ala D Ala probes(Biotin linker Lys(Ac) D Ala D Lactate and 125 I linker Lys(Ac) D Ala D Lactate)respectively,meanwhile,designed and synthesized 18 conformational constrained peptides,peptide derivative libraries and further developed an orthogonal screening approach of "one bead one compound" combinatorial technology.Results Identified a new peptide derivative actively against the low level vancomycin resistant(Enterococcus faecalis,ATCC 51299)with MIC 17 5 mg/L and vancomycin sensitive cell line(Staphylococcus aurreus,ATCC 25923)with MIC 6 25 mg/L respectively.Conclusion The "one bead one compound" combinatorial method can be applied to the study on the interactions between small molecular weight compounds.