Small Peptides as Biotherapeutics

Peptide-based biotherapies have emerged as a significant class of therapeutics due to their ability to modulate various biological processes through interactions with specific targets, such as receptors, enzymes, or proteins. Peptides are small molecules that can be naturally synthesized in different organisms, derived from in vitro enzymatic hydrolysis of food protein, or synthetically designed to mimic endogenous molecules. These last peptides can be modified to improve their biological functions, which makes them versatile tools as biotherapeutics. In this section, we focus on the use of peptides and peptidomimetic derivatives as biotherapeutics in diseases and pathologies associated with proteolytic enzymes, and the obtaining of bioactive peptides derived from the hydrolysis of food proteins, and on their potential use as antihypertensive, antioxidant, and antibacterial agents. Proteolytic enzymes play an important role in numerous physiological functions; however, their overexpression or dysregulated activity can trigger a wide range of diseases and infections, including cardiovascular disorders; immunological-, inflammatory-, and respiratory-conditions; cancer, as well as neurodegenerative disorders like Alzheimer’s disease, among others. Multiple protease inhibitors demonstrated high specific and selective activity in human in vitro and in murine in vivo models, but only a few have been approved as drugs by the U.S. Food & Drug Administration (FDA). In the first part of the section, the major protease inhibitor peptide drugs in the treatment of different pathologies is described. The second part is focused on the bioactive peptides. Bioactive peptides are short sequences of amino acids derived from proteins, which exhibit specific biological activities upon ingestion, absorption, or interaction with target molecules in the body. These peptides can modulate physiological functions such as antimicrobial activity, immunomodulation, antioxidant effects, and regulation of metabolic pathways. Despite bioactive peptides’ promising potential as biotherapeutics, several challenges remain, including stability, immunogenicity, regulatory approval, and manufacturing scalability. Addressing these challenges requires a multidisciplinary approach to advance the development and commercialization of bioactive peptide-based therapies.