Home Blog of Signal Transduction Others Antibiotics for Mammalian Cell Culture Critical Role of Position 10 Residue in the Polymyxin Antimicrobial Activity

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Critical Role of Position 10 Residue in the Polymyxin Antimicrobial Activity

Polymyxins (polymyxin B and colistin) are lipopeptide antibiotics used as a last-line treatment for life-threatening multidrug-resistant (MDR) Gram-negative bacterial infections. Unfortunately, their clinical use has been affected by dose-limiting toxicity and increasing resistance. Structure-activity (SAR) and structure-toxicity (STR) relationships are paramount for the development of safer polymyxins, albeit very little is known about the role of the conserved position 10 threonine (Thr) residue in the polymyxin core scaffold. Here, we synthesized 30 novel analogues of polymyxin B1 modified explicitly at position 10 and examined the antimicrobial activity against Gram-negative bacteria and in vivo toxicity and performed molecular dynamics simulations with bacterial outer membranes. For the first time, this study revealed the stereochemical requirements and role of the β-hydroxy side chain in promoting the correctly folded conformation of the polymyxin that drives outer membrane penetration and antibacterial activity. These findings provide essential information for developing safer and more efficacious new-generation polymyxin antibiotics.

 

Comments：

The study synthesized 30 new polymyxin B1 analogues and found that the stereochemical requirements and role of the β-hydroxy side chain in promoting the correct folding of the polymyxin scaffold drives outer membrane penetration and antibacterial activity, providing essential information for developing safer and more efficacious new-generation polymyxin antibiotics.

Related Products

Cat.No. Product Name Information
S1395 Polymyxin B sulphate Polymyxin B (Aerosporin, PMB, Poly-RX) is an antibiotic primarily used for resistant gram-negative infections.

Related Targets

Antibiotics for Mammalian Cell Culture Antibiotics Antineoplastic and Immunosuppressive Antibiotics