Selective chemical modifications of polymyxin B

Structure−Activity Relationships of Polymyxin Antibiotics

“…Weinstein et al106 employed tetra-Boc PMB as starting material to prepare a series of analogues selectively modified at the Dab1 and Dab9 N γ -amino side chain groups (131–151) . Monofunctionalization of PMB at the Dab1 and Dab9 positions was achieved by protection of the most basic Dab N γ -amino groups (Dab1 and Dab9) by protonation with strong acids while introducing protecting Boc groups on the remaining Dab N γ -amino groups.…”

Antibacterial Mechanisms of Polymyxin and Bacterial Resistance

“…The Dab on polymyxin has three important features, including cationic character of side chain groups, two-methylene group of Dab side chain, and specific order of Dab residues within the primary sequence that gives the proper spatial distribution of positive charge [ 9 ]. Various synthetic or semisynthetic modifications have been applied to Dab in order to increase antimicrobial activity or minimize potential toxicity [ 24 , 25 ]. The N γ -benzyl derivatives of polymyxin B and polymyxin E were synthesized by substituting Dab sides with lipophilic groups.…”

“…Because of the reduced cationic character, the N γ -benzyl derivatives appeared to have higher activity against Gram-positive Staphylococcus aureus and lower activity against Gram-negative E. coli [ 24 ]. The polymyxin B derivatives with positively charged or polar side chain on modified Dab showed better antimicrobial activity than polymyxin B and broadened the antibacterial spectrum [ 25 ]. It has been found thatthe Dabs within the heptapeptide ring on polymyxin B were more critical than the ones in linear tripeptide segment for antimicrobial activity [ 26 ].…”

Facile synthesis of Nα‐protected‐l‐α,γ‐diaminobutyric acids mediated by polymer‐supported hypervalent iodine reagent in water

“…Furthermore, we successfully demonstrated the chemical synthesis of PMBH. Since structure–activity relationship (SAR) of PMB and related peptides has been extensively studied by many researchers (20–26, 29, 30), our method for synthesizing Dab derivatives will contribute to further studies of these peptides. Synthesis of novel PMB analogues is in progress in our laboratory.…”