Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

Abstract

More than 3000 antimicrobial peptides (AMPs) have been discovered, seven of which have been approved by the U.S. Food and Drug Administration (FDA). Now commercialized, these seven peptides have mostly been utilized for topical medications, though some have been injected into the body to treat severe bacterial infections. To understand the translational potential for AMPs, we analyzed FDA-approved drugs in the FDA drug database. We examined their physicochemical properties, secondary structures, and mechanisms of action, and compared them with the peptides in the AMP database. All FDA-approved AMPs were discovered in Gram-positive soil bacteria, and 98% of known AMPs also come from natural sources (skin secretions of frogs and toxins from different species). However, AMPs can have undesirable properties as drugs, including instability and toxicity. Thus, the design and construction of effective AMPs require an understanding of the mechanisms of known peptides and their effects on the human body. This review provides an overview to guide the development of AMPs that can potentially be used as antimicrobial drugs.

Characterization of Cetacean Proline-Rich Antimicrobial Peptides Displaying Activity against ESKAPE Pathogens

“…A large number of antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), have been identified as components of the innate immune systems of animals and plants. Despite difficulties in transiting through the clinical pipeline, AMPs have been widely recognized to have a major potential as anti-infective drug candidates [ 7 , 8 , 9 , 10 ]. This stems from their wide spectrum of activity and from mechanisms of action that are different to those of clinically relevant antibiotics, thus, they are considered to be less prone to be affected by microbial resistance(s) [ 11 , 12 , 13 ].…”

A Novel Peptide Antibiotic, Pro10-1D, Designed from Insect Defensin Shows Antibacterial and Anti-Inflammatory Activities in Sepsis Models

“…To improve the therapeutic potential of AMPs against gram-negative bacteria, it is necessary to optimize the properties of AMPs [ 43 ]. Increased net charge can enhance antimicrobial activity through electrostatic interactions with the negatively charged gram-negative bacterial membranes.…”

An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections

“…The main hurdle of AMPs is their short elimination half-life due to their fast degradation in the presence of proteases once in the blood stream [43]. Therefore, most of the currently used AMPs are directed for topical delivery, especially to wounds.…”

“…As the main focus of this review is on the topical application of AMPs, we considered AMPs, which are in their preclinical and clinical trials development stage, as well those routinely used FDA-approved AMPs and potent AMPs for topical wound infections, which possess antibacterial or in specific cases antifungal activity ( Table 2). The main hurdle of AMPs is their short elimination half-life due to their fast degradation in the presence of proteases once in the blood stream [43]. Therefore, most of the currently used AMPs are directed for topical delivery, especially to wounds.…”