Host defense peptides (HDPs) comprise a heterogeneous group of evolutionarily conserved
and biologically active small molecules that are produced by different organisms. HDPs are widely
researched because they often have multiple biological activities, for example antimicrobial, immunomodulatory
and anticancer activity. In this context, in this review we focus on cryptic HDPs, molecules
derived specifically from proteolytic processing of endogenous precursor proteins. Here, we explore the
biological activity of such molecules and we further discuss the development of optimized sequences
based on these natural cryptic HDPs. In addition, we present clinical-phase studies of cryptic HDPs
(natural or optimized), and point out the possible applicability of these molecules in medicinal chemistry.
Keywords: Cryptic peptides, Bioactive peptides, HDPs, Precursor protein, Optimized HDPs, Cryptic HDPs.
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