Bagheri Mojtaba, Hancock Robert E W
Peptide Chemistry Laboratory, Institute of Biochemistry and Biophysics, University of Tehran, 16 Azar Street, 1417614335, Tehran, Iran.
Department of Microbiology and Immunology, Center forMicrobial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
Methods Mol Biol. 2017;1548:61-71. doi: 10.1007/978-1-4939-6737-7_5.
The emergence of multiresistant bacteria worldwide together with the shortage of effective antibiotics in the market emphasizes the need for the design and development of the promising agents for the treatment of superbug-associated infections. Antimicrobial peptides (AMPs) have been considered as excellent candidates to tackle this issue, and thousands of peptides of different lengths, amino acid compositions, and mode of action have been discovered and prepared to date. Nevertheless, it is of great importance to develop innovative formulation strategies for delivering these AMPs and to improve their low bioavailability and metabolic stability, particularly against proteases, if these peptides are to find applications in the clinic and administered orally or parenterally or used as dietary supplements. The purpose of this chapter is to describe basic experimental principles, based on analytical reversed-phase high-performance liquid chromatography (RP-HPLC) and mass spectrometry (MS), for the prospective design of orally bioavailable AMPs considering the structural characteristics of the peptides and the substrate specificity of proteases that abound in the body especially at sites of infection.
全球范围内多重耐药细菌的出现以及市场上有效抗生素的短缺，凸显了设计和开发有前景的药物以治疗超级细菌相关感染的必要性。抗菌肽（AMPs）被认为是解决这一问题的优秀候选者，迄今为止，已经发现并制备了数千种不同长度、氨基酸组成和作用方式的肽。然而，如果这些肽要应用于临床，通过口服、肠胃外给药或用作膳食补充剂，那么开发创新的给药策略以递送这些抗菌肽并提高其低生物利用度和代谢稳定性，尤其是抵抗蛋白酶的稳定性，就显得至关重要。本章的目的是描述基于反相高效液相色谱（RP-HPLC）和质谱（MS）的基本实验原理，以便根据肽的结构特征以及体内尤其是感染部位大量存在的蛋白酶的底物特异性，对口服生物可利用的抗菌肽进行前瞻性设计。
