Cryptic Host Defense Peptides: Multifaceted Activity and Prospects for Medicinal Chemistry

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.