Designing short bioactive peptides involves identifying minimal sequences that retain or enhance desired biological activities, such as antimicrobial, anticancer, or signalling functions. One common strategy in rational design is to use known motifs by deriving short, functional segments from larger proteins or previously characterized bioactive peptides. This approach ensures that the core activity is preserved while minimizing peptide length. Residue selection is also crucial; amino acids are chosen based on properties that support the desired function—for example, cationic and amphipathic residues such as arginine and lysine are commonly used in designing antimicrobial peptides (AMPs) due to their ability to interact with and disrupt microbial membranes. Additionally, the length of the peptide is also a key design factor, with most bioactive peptides falling within the 5 to 30 amino acid range. The new peptide sequence pursuits to strike a balance between functionality, stability, and ease of synthesis.
In this communication, two bioactive peptides will be presented: one derived from a natural protein sequence and another entirely designed de novo. Also, the pros and cons of branching these short peptides will be discussed at the same time that a new branching connector will be presented, demonstrating the advantages of moving away from the traditional Lys core.