Yan H, Cheng X, He B
Institute of Polymer Chemistry, State Key Laboratory of Functional Polymer Materials for Adsorption and Separation, Nankai University, Tianjin, People's Republic of China.
Biophys Chem. 1998 Aug 24;74(2):107-15. doi: 10.1016/s0301-4622(98)00172-0.
The vancomycin group of antibiotics is considered to act by binding the bacterial cell wall mucopeptide precursor terminating in -L-Lys-D-Ala-D-Ala. The dimerization of these antibiotics is also believed to play a role in the action. In this paper, we analyzed the equilibria in the in vitro antibacterial activity test of the vancomycin antibiotics both with and without the cell wall precursor analogue di-acetyl-L-Lys-D-Ala-D-Ala (DALAA). Based on the equilibria and concentration balance, we obtained 10 equations (seven quadratic equations and three linear equations) containing 10 equilibrium concentrations which relate to the antibiotic, cell wall precursor and DALAA. A computer program was written to solve these equations from known dimerization constant and the binding constants (both monomer and dimer) with DALAA of the antibiotic. The concentrations in the test for vancomycin and eremomycin were obtained. The antibiotic activity of these antibiotics may be quantitatively correlated with their dimerization constants and the binding constants through the calculation. By analyzing the calculated results, we concluded that the cell wall-bound dimer may be the major contributor to the antibiotic activity in the case of eremomycin, while the cell wall-bound monomer is possibly the determinant for the activity of vancomycin.
万古霉素类抗生素被认为是通过与以-L-赖氨酸-D-丙氨酸-D-丙氨酸结尾的细菌细胞壁粘肽前体结合来发挥作用的。这些抗生素的二聚化也被认为在其作用过程中发挥作用。在本文中，我们分析了在有无细胞壁前体类似物二乙酰-L-赖氨酸-D-丙氨酸-D-丙氨酸（DALAA）的情况下，万古霉素类抗生素体外抗菌活性试验中的平衡情况。基于这些平衡和浓度平衡，我们得到了10个方程（7个二次方程和3个线性方程），其中包含与抗生素、细胞壁前体和DALAA相关的10个平衡浓度。编写了一个计算机程序，根据已知的二聚化常数以及抗生素与DALAA的结合常数（单体和二聚体）来求解这些方程。得到了万古霉素和埃瑞霉素试验中的浓度。通过计算，这些抗生素的抗菌活性可能与其二聚化常数和结合常数存在定量相关性。通过分析计算结果，我们得出结论，在埃瑞霉素的情况下，与细胞壁结合的二聚体可能是抗菌活性的主要贡献者，而与细胞壁结合的单体可能是万古霉素活性的决定因素。
