Ongey Elvis Legala, Yassi Hüseyin, Pflugmacher Stephan, Neubauer Peter
Chair of Bioprocess Engineering, Department of Biotechnology, Technische Universität Berlin, Ackerstraße 76, ACK24, 13355, Berlin, Germany.
Department of Biotechnology, Technische Universität Berlin, Ackerstraße 76, ACK24, 13355, Berlin, Germany.
Biotechnol Lett. 2017 Apr;39(4):473-482. doi: 10.1007/s10529-016-2279-9. Epub 2017 Jan 2.
The intrinsic qualities of lanthipeptides for their use as therapeutic drugs present several challenges because of their properties, which include stability, solubility and bioavailability, which, under physiological conditions, are very low. Researches have encouraged clinical evaluation of a few compounds, such as mutacin 1140, microbisporicin, actagardine and duramycin, with pharmacokinetic profiles showing rapid distribution and elimination rates, good bioavailability and fecal excretion, as well as high protein binding. Local and parenteral administration are currently suitable to minimize environmental influences on lanthipeptides and ensure efficient activity. Nevertheless, valuable improvements on pharmacodynamic and pharmacokinetic properties may also permit systemic applications via enteral routes. Understanding how rational modifications influence the desired pharmacological and pharmacokinetic properties of these biomolecules would help to answer some specific questions about their susceptibility to environmental changes, mechanism of action and how to engineer other peptides of the same group to improve their clinical relevance.
由于羊毛硫肽用作治疗药物的内在特性，其稳定性、溶解性和生物利用度等性质在生理条件下非常低，这给其作为治疗药物带来了诸多挑战。研究人员已推动对一些化合物进行临床评估，如变链菌素1140、微双孢菌素、放线嘉丁菌素和耐久霉素，这些化合物的药代动力学特征显示出快速的分布和消除速率、良好的生物利用度和粪便排泄，以及高蛋白结合率。目前，局部和肠胃外给药适合将环境对羊毛硫肽的影响降至最低并确保有效活性。然而，药效学和药代动力学性质的显著改善也可能允许通过肠内途径进行全身应用。了解合理修饰如何影响这些生物分子所需的药理和药代动力学性质，将有助于回答一些关于它们对环境变化的敏感性、作用机制以及如何改造同一组中的其他肽以提高其临床相关性的具体问题。
