Long R3 IGF-I (link:https://www.bloomtechz.com/synthetic-chemical/peptide/long-r3-igf-i-cas-143045-27-6.html) is a synthetic polypeptide molecule whose discovery history began in the 1970s. At that time, researchers began to pay attention to the important role of endogenous insulin-like growth factor-I (IGF-I) in controlling growth and metabolism, and tried to design a molecular structure similar to IGF-I but more biological and pharmaceutical A new type of peptide molecule with application value.
1. The discovery and research of IGF-I:
In the early 1950s, researchers began to explore the existence and function of insulin-like growth factors. In the 1960s, some research organizations isolated a new type of protein with cell proliferation and growth-promoting activity from animal serum, called growth hormone (GH). Later, researchers discovered another protein closely related to GH from animal serum and other tissues, called IGF-I.
IGF-I is a small molecular protein consisting of 70 amino acid residues, and its structure is similar to human insulin. IGF-I is mainly synthesized by the liver, which is closely related to the physiological effects of GH, and can regulate cell proliferation, differentiation and metabolism through the interaction between its own receptors and insulin-like growth factor receptor (IGF-IR).
In the 1970s, as the research on IGF-I deepened, researchers began to explore its molecular structure and biological properties, and tried to develop a more valuable IGF-I analog molecule.
2. Discovery and research of long R3 IGF-I:
From the late 1970s to the early 1980s, some researchers began to modify the N-terminal sequence of IGF-I and designed an IGF-I analog with a more stable molecular structure and easier synthesis and use. On this basis, long R3 IGF-I was born.
Long R3 IGF-I uses arabinosyl-Ala-Pro-Ala (Apa) to replace the Gln-Pro-Arg-Gly sequence of endogenous IGF-I, resulting in a longer half-life in plasma, and Not easily bound and cleared by IGF-binding protein (IGFBP). In addition, the long R3 IGF-I was also modified by adding 13 amino acid sequences (including Arg-Lys-Glu-Gly-Ser) at the C-terminus, introducing disulfide bonds and α-helical structures, etc., so that it has a higher biological activity and potential for pharmaceutical application.
During the research and development of long R3 IGF-I, some researchers also tried to improve its expression efficiency and production cost through transgenic technology and other means. For example, long R3 IGF-I was expressed by microbial systems such as Escherichia coli and yeast, and purified and separated by acid treatment, countercurrent chromatography and other technologies, and finally a high-purity long R3 IGF-I product was obtained.
During the long research process, according to the special structure of LONG R3 IGF-I, which is a polypeptide molecule similar in structure to endogenous IGF-I and has an additional 13 amino acids, various synthetic methods have been studied for production. The preparation process of long R3 IGF-I mainly has the following methods:
1. Chemical synthesis method:
Chemical synthesis is one of the most commonly used methods for preparing long R3 IGF-I. The chemical synthesis of long R3 IGF-I was carried out based on the known amino acid sequence of IGF-I, and an additional 13 amino acid sequences added at the N-terminus of long R3 IGF-I. Synthesis requires the use of multiple protecting groups to ensure amino acid selectivity and reaction efficiency. Usually, the protected peptide segment of the target amino acid is first prepared by solid-phase synthesis, and then assembled into a long R3 IGF-I molecule by liquid-phase synthesis.
2. Biotechnology Act:
The biotechnology method mainly uses engineered cells to express recombinant proteins, and expresses LONG R3 IGF-I by changing gene sequences and expression vectors. In this method, the LONG R3 IGF-I gene can be introduced into the host cell for expression by gene recombination technology, lentiviral vector, plasmid vector and the like. This method can produce a large amount of LONG R3 IGF-I, and can also optimize its expression and purification effect by changing the vector and secretion signal sequence.
3. Enzymatic method:
The enzymatic method mainly uses specific enzymes such as pepsin and clam muscle enzyme to cleave the long R3 IGF-I precursor protein to obtain the LONG R3 IGF-I monomer, while avoiding unnecessary by-products. In this method, the matrix containing the long R3 IGF-I precursor protein needs to be obtained first, and then reacted at an appropriate temperature by adding enzymes and pH control, etc., to finally obtain the target substance LONG R3 IGF-I.
4. Protein modification method:
The protein modification method mainly uses the synthesized endogenous IGF-I to modify it to achieve the effect of long R3 IGF-I. In this method, the N-terminal of endogenous IGF-I is usually introduced into 13 specific sequences to make it have the effect of long R3 IGF-I. In addition, the biological activity and half-life of long R3 IGF-I can be further improved by changing the C-terminal group.
To sum up, the synthesis methods of long R3 IGF-I include chemical synthesis, biotechnology, enzymatic and protein modification, and each method has its advantages, disadvantages and scope of application. With the continuous development of chemical synthesis technology, genetic engineering technology and other fields, the preparation technology of long R3 IGF-I will also be further improved and improved.