Semi-synthesis of Polymyxin B (2-10) and Colistin (2-10) Analogs Employing the Trichloroethoxycarbonyl (Troc) Group for Side Chain Protection of .ALPHA.,.GAMMA.-Diaminobutyric Acid Residues

Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis

“…Recently, total or semisynthesis or modifications of polymyxins was performed chemically or enzymatically, and the resulting products were effectively used for structure-function study (6,20,36,45,50,52). There is a limitation to obtaining diverse derivatives by using chemical or enzymatic approaches, however, and this limitation is related to the structural complexity of polymyxin.…”

Contribution of Each Amino Acid Residue in Polymyxin B3 to Antimicrobial and Lipopolysaccharide Binding Activity

“…We previously reported a study aimed at clarifying the contribution of the N-terminal fatty acyl groups of various polymyxin B family peptides to biological activity, as well as the development of N-terminal analogs without fatty acyl groups. 16,18,19) The aim of the present study was to clarify the structural requirements of the side chain of each amino acid residue by means of alanine scanning, and to further examine the role of the hydrophobic portion (D-Phe-Leu) of the polymyxin B 3 lactam ring in antimicrobial activity and LPS binding, employing sixteen synthetic peptides (Fig. 1).…”

Development of Des-Fatty Acyl-Polymyxin B Decapeptide Analogs with Pseudomonas aeruginosa-Specific Antimicrobial Activity

“…7 ]-PMB (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) activity of 10 and 11 was not reflected in their bactericidal potency against E. coli, which was moderate, with MIC values of 8 and 16 nmol/ml, respectively (Table 3, Fig. 3B).…”

“…7) Our previous studies on the structureantimicrobial activity relationship of PMB showed that desfatty acyl-PMB (Des-FA-[Dab 1 ]-PMB) has considerable antimicrobial activity, with MIC values of 8, 16 and 4 nmol/ml against E. coli, Salmonella Typhimurium (S. Typhimurium) and Pseudomonas aeruginosa (P. aeruginosa). [7][8][9] Apparently, the introduction of Dab at the N-terminal of PMBN greatly increases its activity towards E. coli, from an MIC value of 256 to 8 nmol/ml. We therefore selected the cyclic decapeptide Des-FA- [Dab 1 ]-PMB as a lead compound for developing a peptide antibiotic with increased antimicrobial activity and decreased toxicity.…”