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Chemical Structure of Peptides
Peptides usually refer to peptide chains composed of no more than 50 amino acids, between small molecule drugs (molecular weight<500) and protein drugs (molecular weight>5000).
Due to the involvement of peptides as signaling molecules in numerous physiological functions within the body, peptide drugs often serve as alternative therapies to compensate for the lack of endogenous peptide hormone levels.
From the isolation and extraction of early animal tissues to modern artificial synthesis, peptide drugs have been widely recognized and widely used in clinical treatment. Research peptides, crucial intermediates in drug development, have significantly accelerated the evolution of therapeutic strategies across various medical fields.
Research has found that regardless of the period, the number of research and development projects for natural peptides has always been small, and the enthusiasm for peptide analogues has never decreased. However, the number of heterologous peptides has been increasing since 2000, which indirectly reflects the development and changes in peptide synthesis technology:
What is Peptide Synthesis Technology?
Peptide synthesis (peptide chain synthesis) essentially involves arranging amino acid units according to the structural rules of natural amino acids. To synthesize peptides in a specific order, the directed peptide synthesis method can only be used, which involves protecting the amino or carboxyl groups that do not require a reaction with appropriate groups before proceeding with the linking reaction.
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At present, the main methods for peptide synthesis are chemical and biological methods. The biosynthesis of peptides mainly involves fermentation and enzymatic hydrolysis. With the development of biotechnology, genetic engineering methods led by DNA recombination technology have also been applied to the synthesis of peptides.
Peptide Length is No Longer a Challenge in Peptide R&D
In the 1980s, almost all clinical trial stages had peptides with lengths less than 10 amino acids. In the following decade, the average length of peptides gradually increased, mainly due to the improvement and maturity of peptide synthesis technology.
At present, long peptide chains up to 40 amino acids have also been successfully developed, indicating that peptide chain length is no longer a challenge in peptide drug development.
From natural extraction to artificial synthesis, peptides, as a new class of drugs, have shown unique advantages in clinical application and production preparation.
Firstly, in clinical practice, it is similar to recombinant protein drugs and monoclonal antibodies, with advantages such as strong specificity and good efficacy; Secondly, peptide drugs are similar in production and preparation to small molecule drugs, with characteristics such as high purity, controllable quality, and easy determination of structure. Therefore, peptide therapy is currently considered a highly selective, effective, and relatively safe potential therapy.
Peptide Therapy is Not Flawless
Although peptide therapy has promising prospects, it is not flawless either. Due to the presence of peptidases, the half-life of peptide hormones is usually short, and this instability has a negative impact on drug development and treatment.
Another technical bottleneck of peptides is the low oral utilization rate. In recent years, a new peptide synthesis strategy has emerged to overcome the aforementioned technical challenges.
Researchers can reduce the injection frequency of peptide drugs and improve their stability and other physical properties by adjusting pharmacokinetic characteristics, modifying amino acid frameworks, incorporating non-natural amino acids, conjugating groups that extend half-life, and improving solubility.
Peptide Drug Conjugates
Among peptide modification, conjugated binding groups have become an important means of changing the properties of peptide drugs. Since 2010, approximately 30% of peptide drugs in clinical trials worldwide have been conjugates , such as structural conjugates with polyethylene glycol, lipids, and proteins.
Research has shown that conjugating Fc fragments can prolong the half-life of peptides, and peptide drug conjugates can also be used as payloads and transporters for cytotoxic agents. Some common peptide drug conjugates are shown in table：
Proportion of peptide drug conjugates in different clinical trial stages：
Growth Rate of Peptide Drug Market
From a market perspective, the global peptide drug market has seen a compound growth rate of over 12% in recent years, with a market size approaching $20 billion. According to Transparency Market Research, a consulting firm, the global peptide drug market reached $23.7 billion in 2022.
The overall peptide drug market is in an upward trend of development and has become an important direction for new drug research and development by pharmaceutical companies worldwide. Large multinational pharmaceutical companies such as pharmaceutical giants Pfizer, Merck, Roche, Lilly, Novartis, Sanofi, and Bayer have all increased their investment in peptide drug research and development through acquisitions or mergers, and have successively harvested many listed drugs.
Global representative heavyweight peptide drugs include Liraglutide, Duraglutide, Glatirameracetate, Leuprorelin acetate, Octreotide acetate, Goserelin, and Exenatide.
Indications for Peptide: Most Anti-tumor Drugs
According to the Cortellis database, as of May 7, 2022, there are 1153 types of peptide synthetic drugs worldwide, and 198 types of peptide drugs were launched in 2022. Their indications are wide, including tumors, cardiovascular diseases, major endocrine and metabolic diseases, or more common diseases, among which the number of drugs targeting tumors is the highest.
Summary
Overall, peptide drugs have many advantages over traditional drugs, and the global clinical market demand is increasing. It can be foreseen that with the progress of modern synthesis technology, more and more new peptide drugs will be launched in the future, bringing good news to the vast number of patients.
