Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1971 Aug;123(5):789–803. doi: 10.1042/bj1230789

Modifications of the acyl-d-alanyl-d-alanine terminus affecting complex-formation with vancomycin

M Nieto 1, H R Perkins 1
PMCID: PMC1177079  PMID: 5124386

Abstract

Vancomycin forms complexes with peptides terminating in d-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 the d-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 an l-configuration was somewhat better than a d-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 terminal d-residue may form the cross-link in mucopeptide structure) and acyl-l-alanyl-d-glutamylglycine (a sequence found in the mucopeptide of Micrococcus lysodeikticus and related organisms). These results throw some light on the specificity of the uptake of vancomycin by living bacteria.

Full text

PDF
789

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BREITENBACH J. W., DERKOSCH J., WESSELY F. Energetics of peptide formation. Nature. 1952 May 31;169(4309):922–922. doi: 10.1038/169922a0. [DOI] [PubMed] [Google Scholar]
  2. Chatterjee A. N., Perkins H. R. Compounds formed between nucleotides related to the biosynthesis of bacterial cell wall and vancomycin. Biochem Biophys Res Commun. 1966 Aug 12;24(3):489–494. doi: 10.1016/0006-291x(66)90188-4. [DOI] [PubMed] [Google Scholar]
  3. Ghuysen J. M., Leyh-Bouille M., Bonaly R., Nieto M., Perkins H. R., Schleifer K. H., Kandler O. Isolation of DD carboxypeptidase from Streptomyces albus G culture filtrates. Biochemistry. 1970 Jul 21;9(15):2955–2961. doi: 10.1021/bi00817a004. [DOI] [PubMed] [Google Scholar]
  4. Ghuysen J. M. Use of bacteriolytic enzymes in determination of wall structure and their role in cell metabolism. Bacteriol Rev. 1968 Dec;32(4 Pt 2):425–464. [PMC free article] [PubMed] [Google Scholar]
  5. Hughes R. C. Autolysis of isolated cell walls of Bacillus licheniformis N.C.T.C. 6346 and Bacillus subtilis Marburg Strain 168. Separation of the products and characterization of the mucopeptide fragments. Biochem J. 1970 Oct;119(5):849–860. doi: 10.1042/bj1190849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. ITO E., STROMINGER J. L. ENZYMATIC SYNTHESIS OF THE PEPTIDE IN BACTERIAL URIDINE NUCLEOTIDES. III. PURIFICATION AND PROPERTIES OF L-LYSIN-ADDING ENZYME. J Biol Chem. 1964 Jan;239:210–214. [PubMed] [Google Scholar]
  7. Krumdieck C. L., Baugh C. M. The solid-phase synthesis of polyglutamates of folic acid. Biochemistry. 1969 Apr;8(4):1568–1572. doi: 10.1021/bi00832a036. [DOI] [PubMed] [Google Scholar]
  8. LEVY A. L. A paper chromatographic method for the quantitative estimation of amino-acids. Nature. 1954 Jul 17;174(4420):126–127. doi: 10.1038/174126a0. [DOI] [PubMed] [Google Scholar]
  9. Leyh-Bouille M., Ghuysen J. M., Bonaly R., Nieto M., Perkins H. R., Schleifer K. H., Kandler O. Substrate requirements of the Streptomyces albus G DD carboxypeptidase. Biochemistry. 1970 Jul 21;9(15):2961–2970. doi: 10.1021/bi00817a005. [DOI] [PubMed] [Google Scholar]
  10. Leyh-Bouille M., Ghuysen J. M., Nieto M., Perkins H. R., Schleifer K. H., Kandler O. On the Streptomyces albus G DD carboxypeptidase mechanism of action of penicillin, vancomycin, and ristocetin. Biochemistry. 1970 Jul 21;9(15):2971–2975. doi: 10.1021/bi00817a006. [DOI] [PubMed] [Google Scholar]
  11. NEWTON G. G., ABRAHAM E. P. Degradation, structure and some derivatives of cephalosporin N. Biochem J. 1954 Sep;58(1):103–111. doi: 10.1042/bj0580103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Neuberger A., Sanger F. The availability of the acetyl derivatives of lysine for growth. Biochem J. 1943 Oct;37(4):515–518. doi: 10.1042/bj0370515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nieto M., Perkins H. R. Physicochemical properties of vancomycin and iodovancomycin and their complexes with diacetyl-L-lysyl-D-alanyl-D-alanine. Biochem J. 1971 Aug;123(5):773–787. doi: 10.1042/bj1230773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ondetti M. A., Deer A., Sheehan J. T., Pluscec J., Kocy O. Side reactions in the synthesis of peptides containing the aspartyglycyl sequence. Biochemistry. 1968 Nov;7(11):4069–4075. doi: 10.1021/bi00851a040. [DOI] [PubMed] [Google Scholar]
  15. Perkins H. R., Nieto M. The preparation of iodinated vancomycin and its distribution in bacteria treated with the antibiotic. Biochem J. 1970 Jan;116(1):83–92. doi: 10.1042/bj1160083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Perkins H. R. Specificity of combination between mucopeptide precursors and vancomycin or ristocetin. Biochem J. 1969 Jan;111(2):195–205. doi: 10.1042/bj1110195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schnabel E. Verbesserte Synthese von tert.-Butyloxycarbonyl-aminosäuren durch pH-Stat-Reaktion. Justus Liebigs Ann Chem. 1967;702:188–196. doi: 10.1002/jlac.19677020123. [DOI] [PubMed] [Google Scholar]
  18. Smith G. F., Murray M. Direct spectrophotometric quantitation of phenylthiohydantoin derivatives of amino acids from thin layers of silica gel. Anal Biochem. 1968 May;23(2):183–195. doi: 10.1016/0003-2697(68)90350-3. [DOI] [PubMed] [Google Scholar]
  19. Stewart J. M., Young J. D., Benjamini E., Shimizu M., Leung C. Y. Immunochemical studies on tobacco mosaic virus protein. IV. The automated solid-phase synthesis of a decapeptide of tobacco mosaic virus protein and its reaction with antibodies to the whole protein. Biochemistry. 1966 Nov;5(11):3396–3400. doi: 10.1021/bi00875a002. [DOI] [PubMed] [Google Scholar]
  20. Tipper D. J., Berman M. F. Structures of the cell wall peptidoglycans of Staphylococcus epidermidis Texas 26 and Staphylococcus aureus Copenhagen. I. Chain length and average sequence of cross-bridge peptides. Biochemistry. 1969 May;8(5):2183–2192. doi: 10.1021/bi00833a060. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES