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The characterisation of novel MccB17 analogues with altered activity may well point to new lead structures and help to identify pharmacophores. In particular, the bis-heterocycles of MccB17 appear to be of major importance
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Sinha Roy R., Kelleher N.L., Milne J.C., Walsh C.T. In vivo processing and antibiotic activity of microcin B17 analogs with varying ring content and altered bisheterocyclic sites. Chem Biol. 6:1999;305-318. The characterisation of novel MccB17 analogues with altered activity may well point to new lead structures and help to identify pharmacophores. In particular, the bis-heterocycles of MccB17 appear to be of major importance.
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Facile methods to approach the synthesis of mimetic structures related to those natural substances described here are needed if combinatorial approaches to new compound design are to be successful. Ozl/Tzl and related structures are logical choices for the investigation of DNA-interacting compounds and offer a new means of restricting conformational freedom and generating additional diversity in peptide mimetics
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•], a relatively complete model for the biosynthesis of MccB17 can finally be envisaged
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•], a relatively complete model for the biosynthesis of MccB17 can finally be envisaged.
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Expressed protein ligation to probe regiospecificity of heterocyclization in the peptide antibiotic microcin B17
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EPL is a relatively new technique allowing the incorporation of, in particular, unusual (i.e. not genetically encoded) amino acids into peptides and proteins in a semi-synthetic manner. The use of EPL to incorporate homocysteine demonstrates the potential of this technique in such studies and shows that the Mccb17 synthetase is reasonably discerning in its choice of substrate. The results fit well with earlier work showing that threonine cannot be substituted in place of serine
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Sinha Roy R., Allen O., Walsh C.T. Expressed protein ligation to probe regiospecificity of heterocyclization in the peptide antibiotic microcin B17. Chem Biol. 6:1999;789-799. EPL is a relatively new technique allowing the incorporation of, in particular, unusual (i.e. not genetically encoded) amino acids into peptides and proteins in a semi-synthetic manner. The use of EPL to incorporate homocysteine demonstrates the potential of this technique in such studies and shows that the Mccb17 synthetase is reasonably discerning in its choice of substrate. The results fit well with earlier work showing that threonine cannot be substituted in place of serine.
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Chem Biol
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Sinha Roy, R.1
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