Polypeptides are biologically active substances involved in various cell functions in organisms. Polypeptide is a compound formed by linking α-amino acids together by peptide bonds, and it is also an intermediate product of protein hydrolysis.
Generally, compounds formed by dehydration and condensation of three or more amino acid molecules can become polypeptides. With the maturity of biotechnology and peptide synthesis technology, more and more peptide drugs have been developed and applied in clinical practice.
Because of its wide indications, high safety, and remarkable efficacy, peptide drugs have been widely used in the prevention, diagnosis and treatment of tumors, hepatitis, diabetes, AIDS and other diseases, and have broad development prospects.
Peptides are easy to synthesize, modify and optimize, and their medicinal value can be quickly determined
Due to its own characteristics, the time from clinical trials to FDA approval of peptides is much shorter than that of small molecule drugs, about 10 years on average. Peptides are twice as likely to pass clinical trials as small molecule compounds. The advantages of peptides make it show unique advantages and clinical application value in drug development.
The half-life of peptides is usually short and unstable
Peptide drugs are easily degraded rapidly in the body. Peptide preparations need to be stored at low temperatures. However, the stability can be improved by modifying or forming a stable composite with other materials. Compared with macromolecular proteins or antibodies, peptides are more stable at room temperature, with less dosage and higher unit activity.
Compared with macromolecular proteins, peptide synthesis technology is mature
Peptides are easily separated from impurities or by-products with high purity. The quality, purity and yield of recombinant protein are difficult to guarantee. Recombinant proteins cannot introduce unnatural amino acids, nor can they be amidated at the ends. At the same time, the production cycle is long and the cost is high. Peptides are generally cheaper than protein antibody drugs, but more expensive than many small molecule drugs. The synthesis cost of long-chain peptides will be higher, but with the advancement of science and technology, equipment updates and technological improvements, the synthesis and commercialization costs of small molecule peptides have been greatly reduced, making them more suitable for clinical applications and market development.
Peptide drugs cannot be taken orally
Polypeptide drugs are easily degraded and difficult to pass through the intestinal mucosa, so they cannot be taken orally. But it can be administered by other routes, such as subcutaneous injection and nasal spray.
Low dose, strong selectivity, good specificity, good curative effect, few side effects
Compared with small molecule drugs, some peptide drugs have the advantages of low dose, strong selectivity, good specificity, good curative effect, and fewer side effects.
Many small molecular compounds accumulate in specific organs of the human body, and large molecular proteins or antibodies will be non-specifically absorbed by the reticuloendothelial system and liver, which will inevitably produce side effects of varying degrees, and some side effects will be very serious.
Polypeptides usually have no or minimal side effects. The main reason is that the degradation products of small peptides are amino acids, which generally do not accumulate in specific organs and tissues, and are easily excreted from the body through the liver and kidneys.
Therefore, there are almost no toxicological problems caused by foreign body metabolism. However, some of them may have side effects due to excessive doses or inflammation or other reactions at the injection site due to injection.
Peptides lack cell membrane permeability, which affects cell absorption
Due to the size, polarity, hydrophilicity and chargeability of peptides, it is difficult to cross cell membranes, physiological barriers and blood-brain barriers.
However, there is a class of cell-penetrating polypeptides that have strong cell membrane permeability, so they are used as drug carriers to help drugs pass through cell membranes.
At the same time, some polypeptides can be used as non-specific small-molecule drug targeting carriers to deliver drugs to tumor cells and other specific receptor target cells through specific receptors on the cell surface.
In the pharmaceutical industry, peptides and polypeptides can be purified by chromatographic columns, and then further concentrated by evaporating vacuum.
Because the peptide concentration is too low and the evaporation time is too long, it may destroy the purified product and consume a large amount of organic/water eluent.
At present, the use of nanofiltration membranes to directly concentrate it can not only overcome the above shortcomings, but also remove small molecular organics and salts.