Antibiotics

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

“…The cyclization reaction proceeded quantitatively in a high concentration (ca. 0.01 mmol/ml) solution of 1 L -16 L to yield 1 C -16 C , which were treated with HF to yield polymyxin B analogs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The purity of the synthetic peptides was Ͼ97% as shown representatively in Fig.…”

“…1,2) Polymyxin B contains six a,g-diaminobutyric acid (Dab) residues. The gamino group of Dab 4 is acylated by C-terminal Thr 10 to form a 23-member lactam ring 3,4) resulting in a peptide that has antimicrobial activity against Gram-negative bacteria.…”

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

“…Polymyxin B (2-10) and colistin (2)(3)(4)(5)(6)(7)(8)(9)(10) are cyclic nonapeptides obtained respectively from polymyxin B and colistin by enzymic removal of fatty acyl-Dab-OH with ficin 13) or papain. 14) The toxicity of the nonapeptides is known to be markedly low in comparisons with the parent compounds, polymyxin B and colistin; however, both nonapeptides are very weak bactericidals despite the fact that they retain considerable binding activity to LPS.…”

“…Tetrakis(N g -Tfa)-polymyxin B (2-10) and tetrakis(N gTfa)-colistin (2)(3)(4)(5)(6)(7)(8)(9)(10), which have N a -free and N g -protected amino functions, were useful starting materials for the semisynthesis of their N-terminal derivatives. However, the yields of tetrakis(N g -Tfa)-polymyxin B (2-10) and tetrakis(N g -Tfa)-colistin (2-10) were only 8-11%.…”

Novel Des-Fatty Acyl-Polymyxin B Derivatives with Pseudomonas aeruginosa-Specific Antimicrobial Activity

“…The other PMB derivatives ( (1), (3) and (4)) were synthesized in a manner similar to that described in (2). Guanylation of the cyclic partially protected peptide was performed in the following manner.…”