Structure–activity relationships of bacterial outer-membrane permeabilizers based on polymyxin B heptapeptides

Mapping residue-specific contacts of polymyxin B with lipopolysaccharide by saturation transfer difference NMR: Insights into outer-membrane disruption and endotoxin neutralization

“…The functional significance, in terms of antimicrobial and LPS neutralization activities of these Dab residues had been evaluated. 42,[73][74][75][76] Results obtained from this work can be correlated with the antimicrobial and anti-endotoxic activities of PMB. AMPs would interact with the LPS layer of the outer membrane causing disruption of the permeability barrier.…”

“…48 Replacements of D-Phe6 and Leu7 with other residues had caused significant loss of antimicrobial activities and LPS binding of PMB. 73,74,76 The N-terminus lipidic MO chain of PMB has been known for its involvement in disruption at the outer membrane and antimicrobial/antiendotoxic activities. 34 The CH 2 and CH 3 groups of MO appear to show different percentage of STD affects in LPS micelles, implying that the entire chain does not have similar proximity with LPS micelles (see Figure 10).…”

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

“…In a previous study we and Urakawa et al found that PMB heptapeptide and its derivatives have no significant antimicrobial activity against Gram-negative bacteria, but the binding activity to LPS is retained. 13,22) Therefore, PMB heptapeptide analogs with better permeability into the outer membranes were designed. Only Guanyl-PMB(4-10) (10), which is the lowest molecular weight analog studied, had antimicrobial activity against P. aeruginosa.…”

Design and syntheses of gramicidin S analogs, cyclo(-X-Leu-X-D-Phe-Pro-)2 (X=His, Lys, Orn, Dab and Dap)

“…On the other hand, in CD spectrum of 5, two troughs were observed near 196 and 220 nm, suggesting that 5 adopts disordered conformation in comparison with those of 1-4. Recently, Urakawa et al 11 reported similar results in studies of cyclic heptapeptides related to polymyxin B. 11 That is, the replacement of Dab residues in cyclic heptapeptides of polymyxin B into Orn and Dap residues influences largely its conformation and antibiotic activity.…”

“…Recently, Urakawa et al 11 reported similar results in studies of cyclic heptapeptides related to polymyxin B. 11 That is, the replacement of Dab residues in cyclic heptapeptides of polymyxin B into Orn and Dap residues influences largely its conformation and antibiotic activity. Design and syntheses of gramicidin S analogs M Tamaki et al…”