Since 1901, peptide molecules first appeared in the academic community in an article by Professor Emil Fischer, the Nobel Prize winner in chemistry, and obtained the exclusive term peptide the following year. Peptide molecules have been active in the field of medicine for more than 100 years. In addition to the continuous creation of traditional hormone drugs such as somaluptide, peptides have a very broad exploration space in the field of anti infection, antibacterial and anti-tumor.
Protein protein interactions (PPIs) play an important role in cell function and have become the main target of drug action in the past two decades. However, for large or flat binding sites, small molecule drugs are difficult to interfere with intracellular PPIs, and macromolecular protein / antibody drugs cannot penetrate cell membrane due to their large molecular weight, and it is difficult to reach these targets .
Polypeptides are compounds between macromolecular proteins and small molecule drugs, which can regulate the biological function of cells. Due to the fact that they are mainly derived from natural polypeptides or natural peptide analogues, their structures and mechanisms of action are usually clear, and many of their properties are between small molecule chemical drugs and macromolecular antibody drugs. Studies have shown that peptides have the advantages of high target affinity, stable efficacy, low immunogenicity, small side effects and strong specificity .
With the development of biotechnology and peptide synthesis technology, more and more peptide drugs have been developed and applied in clinic. Because of its wide indications, high safety and significant curative effect, polypeptide drugs have been widely used in cancer, hepatitis, diabetes, AIDS and other fields, with broad development prospects.
So far, more than 7000 peptides from natural sources have been identified, including various hormones, neurotransmitters, growth factors, enzymes and ligands, which play a key role in human physiology. With the development of science and technology, more and more peptide drugs are modified or modified on the basis of natural peptides. The modified or modified peptides can overcome the instability of natural polypeptides, increase water solubility, reduce side effects, and prolong half-life.
For example, the famous semaglutide was based on the natural human glucagon like peptide (GLP-1), which replaced the 8th and 34th amino acids, and linked the free fatty acids on the 26th Lys to obtain GLP-1 analogues (Fig. 1). Compared with natural GLP-1, somaluptide has a longer action time and a half-life of 7 days .
Figure 1: sequence alignment of somaluptide and GLP-1
At present, there are nearly 100 kinds of peptide drugs approved worldwide. The main treatment fields include tumor, diabetes, infection, immunity, cardiovascular and urinary system. Among them, there are 15 kinds of anti-tumor peptide drugs, which is one of the important application fields of peptides. In addition, there are more than 400 kinds of peptide drugs in clinical trials, and more peptide drugs are in the laboratory research stage .
In 2019, there are 10 polypeptide drugs with more than US $1 billion sold worldwide, including liraglutide, dulaglutide, leuprorelin, semaglutide, octreotide, glatiramer, teriparide, lanreotide and bortezomib And carfilzomib (Fig. 2). With the continuous development of biomedicine, polypeptide drugs have become important diagnostic, preventive and therapeutic drugs in the 21st century.
Figure 2: global sales exceeding $1bn in 2019
In biopharmaceutical experiments, polypeptides can be used as a variety of tool drugs. Due to their medicinal value, peptides can be used for drug administration in cell animals. In addition, peptides are important inhibitors or agonists, and it is difficult to find suitable small molecular compounds as agonists in some signal pathways or targets, and most of them come from hormones or hormone analogues It has the function of opening signal path.
For example, insulin can activate the irs1-pi3k-akt signaling pathway after insulin receptor, and some cytokines such as TNF – α and IL can activate the inflammatory signaling pathway; some peptides are also used in modeling, such as the classic animal hypertension model, using angiotensin II (ANG II).
Targetmol now has more than 1000 new peptide products, including most of the listed drug peptides and antibacterial peptides. In addition, there are various peptide hormones, hormone analogues, enzymes, receptors, cytokines, labeled peptides and so on for research and use by researchers.
Table 1 popular peptide products of targetmol
. Andy Chi-Lung Lee, etal. A Comprehensive Review on Current Advances in Peptide Drug Development andDesign, Int J Mol Sci. 2019 May 14;20(10):2383.
. Li Di, et al. StrategicApproaches to Optimizing Peptide ADME Properties, AAPS J. 2015 Jan; 17(1):134–143.
. Rushikesh Sable, etal. Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealthof Natural Sources for Pharmaceutical Applications, Mar Drugs. 2017 Apr; 15(4):124.
. Minzhi Yu, et al. Battleof GLP-1 Delivery Technologies, Adv Drug Deliv Rev . 2018May;130:113-130.
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