MODIFICATIONS OF ACYL-D-ALANYL-D-ALANINE TERMINUS AFFECTING COMPLEX-FORMATION WITH VANCOMYCIN
MODIFICATIONS OF ACYL-D-ALANYL-D-ALANINE TERMINUS AFFECTING COMPLEX-FORMATION WITH VANCOMYCIN
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DOI：
10.1042/bj1230789
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发表时间：
1971-01-01
影响因子：
4.1
通讯作者：
PERKINS, HR
中科院分区：
文献类型：
--
作者：
NIETO, M;PERKINS, HR
万古霉素与终止丙氨酰-d-丙氨酸的多肽形成复合体，类似于细菌粘肽的生物合成前体。用固相法和常规方法制备了许多合成肽，研究了其形成络合物的特异性。可以得出以下结论：(A)需要三个酰胺键才能形成稳定的络合物；(B)末端的羧基必须是自由的；(C)羧基末端和亚末端残基必须是甘氨酸或三种构型；(D)这些残基中侧链的大小对万古霉素的亲和力有很大影响，每种情况下甲基都是最优的；(E)第三和第四位残基的侧链性质对络合物形成的影响较小，但ANL-构型略好于第三位的ad-构型。除了酰基-d-丙氨酰-d-丙氨酸外，细菌细胞壁中的其他多肽也会与万古霉素结合，尽管结合的强度较小，例如酰基-d-丙氨酰-d-α-氨基酸(其中末端残基可能形成粘肽结构中的交联)和酰基-L-丙氨基-d-谷氨酰甘氨酸(在溶血微球菌和相关生物的粘肽中发现的序列)。这些结果为活细菌吸收万古霉素的特异性提供了一些线索。
Vancomycin forms complexes with peptides terminating ind-alanyl-d-alanine that are analogous to the biosynthetic precursors of bacterial mucopeptides. The specificity of complex-formation has been studied by means of many synthetic peptides, prepared by both solid-phase and conventional methods. The following conclusions can be drawn: (a) three amide linkages are required to form a stable complex; (b) the terminal carboxyl group must be free; (c) the carboxyl terminal and subterminal residues must be either glycine or of thed-configuration; (d) the size of the side chain in these residues greatly influences the affinity for vancomycin, a methyl group being the optimum in each case; (e) the nature of the side chain in the third and fourth residues has a smaller effect on complex-formation, but anl-configuration was somewhat better than ad-configuration in the third position. In addition to acyl-d-alanyl-d-alanine, other peptides that occur in bacterial cell walls will combine with vancomycin, although less strongly, e.g. acyl-d-alanyl-d-α-amino acid (where the terminald-residue may form the cross-link in mucopeptide structure) and acyl-l-alanyl-d-glutamylglycine (a sequence found in the mucopeptide ofMicrococcus lysodeikticusand related organisms). These results throw some light on the specificity of the uptake of vancomycin by living bacteria.