Antimicrobial peptides: therapeutic potentials

Abstract

The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.

Keywords::

• AMPs in drug development
• antimicrobial peptides
• limitations of AMPs
• multidrug resistance
• strategies for new therapeutic drug

Financial & competing interests disclosure

This work was financially supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health Welfare, Republic of Korea (No. A092006), and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2007-0056817, 2012-R1A2A1A01003569). This work was also supported by the 2014 BK21 Plus Project for Medicine, Dentistry and Pharmacy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Abuse of antibiotics leads to the emergence of multidrug-resistant microorganisms, resulting in an urgent necessity for a new class of antibiotics with different mechanisms of action from traditional antibiotics.

• Antimicrobial peptides (AMPs) have been considered as potential therapeutics because of their antibacterial, antifungal, antiviral and even anticancer activities and different mechanisms of action from traditional antibiotics.

• AMPs have some disadvantages such as toxicity, stability and cost issues for their clinical and commercial development.

• Obstacles of AMPs can be overcome through structural modifications or through prodrug formation.

• AMPs are still attractive sources of novel antibiotics to pharmaceutical companies.