It has been said that the 21st century is the century of peptide drugs, and the fate of this substance, which lies between a large protein and a small molecule compound, is bound to be extraordinary.
Compared to chemical drugs, peptides are physicochemically unstable, susceptible to oxidation and hydrolysis, prone to agglomeration, have a shorter half-life, have a faster clearance rate, do not readily cross cell membranes, and most cannot be taken orally.
Then, essential amino acids and possible substitution sites are identified by means of alanine substitution, conformational relationships (SAR) and other analytical methods.
Another important aspect of rational peptide drug design is to improve the physicochemical properties of natural peptides, which often have a tendency to be agglomerated and poorly water-soluble.
Other methods can also be used to improve the stability of peptides, such as the introduction of stable alpha helices, the formation of salt bridges, or other chemical modifications such as lactam bridges.
The second method is to bind the peptide to albumin, which prolongs the half-life of the peptide drug and reduces the frequency of use of the drug, and Liraglutide, which applies this method, is one of the successful examples.