The growing problem of bacterial resistance to conventional antibiotic compounds and the need for new antibiotics have stimulated interest in the development of antimicrobial peptides (AMPs) as human therapeutics. Development of topically applied agents, such as pexiganan (also known as MSI-78, an analog of the naturally occurring magainin2, extracted from the skin of the African frog Xenopus laevis) has been the focus of pharmaceutical development largely because of the relative safety of topical therapy and the uncertainty surrounding the long-term toxicology of any new class of drug administered systemically. The main hurdle that has hindered the development of antimicrobial peptides is that many of the naturally occurring peptides (such as magainin), although active in vitro, are effective in animal models of infection only at very high doses, often close to the toxic doses of the peptide, reflecting an unacceptable margin of safety. Though MSI-78 did not pass the FDA approval, it is still the best-studied AMP to date for therapeutic purposes. Biophysical studies have shown that this peptide is unstructured in solution, forms an antiparallel dimer of amphipathic helices upon binding to the membrane, and disrupts membrane via toroidal-type pore formation. This article covers functional, biophysical, biochemical and structural studies on pexiganan.

细菌对常规抗生素化合物的耐药性日益增长的问题以及对新抗生素的需求，激发了人们对开发抗菌肽（AMPs）作为人类治疗剂的兴趣。从非洲青蛙非洲爪蟾（Xenopus laevis）的皮肤中提取的局部应用药物的开发，例如pexiganan（也称为MSI-78，它是天然存在的magainin2的类似物））一直是药物开发的重点，这是因为局部治疗的相对安全性以及全身性管理的任何新类别药物的长期毒理学都存在不确定性。阻碍抗菌肽发展的主要障碍是，许多天然存在的肽（如magainin）尽管在体外具有活性，但仅在非常高的剂量（通常接近其毒性剂量）的动物感染模型中才有效。肽，反映出不可接受的安全范围。尽管MSI-78没有通过FDA批准，但它仍然是迄今为止在治疗方面研究最好的AMP。生物物理研究表明，该肽在溶液中是非结构化的，与膜结合后会形成两亲螺旋的反平行二聚体，并通过环形孔形成膜。本文涵盖对pexiganan的功能，生物物理，生化和结构研究。