With the continued rise in antibiotic-resistant bacteria, there is an immense need for the development
of new therapeutic agents. Host-defense peptides (HDPs) offer a unique alternative to
many of the current approved antibiotics. By targeting the host rather than the pathogen, HDPs offer
several benefits over traditional small molecule drug treatments, such as a slower propensity towards
resistance, broad-spectrum activity and lower risk of patients developing sepsis. However, natural
peptide structures have many disadvantages as well, including susceptibility to proteolytic degradation,
significant costs of synthesis and host toxicity. For this reason, much work has been done to examine
peptidomimetic structures, in the hopes of finding a structure with all of the desired qualities of
an antibiotic drug. Recently, this research has included synthetic constructs that mimic the behavior of HDPs but have no
structural similarity to peptides. This review article focuses on the progression of this field of research, beginning with an
analysis of a few prominent examples of natural HDPs and moving on to describe how the information learned by studying
them have led to the current design platforms.
Keywords: Antimicrobial, Host-defense peptide, Immunomodulation, Innate-defense regulator, Peptidomimetic, SMAMP.
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