The Research Of Exenatide Synthesis Method

Diabetes is a disease in which the amount of glucose (sugar) in the blood is too high because the body cannot produce or properly use insulin. There are four types of diabetes: Type 1 Diabetes, Type 2 Diabetes. Pre — Diabetes. Gestational Diabetes. Most people who are diagnosed with diabetes have type 2 diabetes. Genetic susceptibility . Hyperinsulin secretion. Insulin resistance. Glucose intolerance and Environmental factors are the major cause of type 2 diabetes. There are 130 million children and adults all over the world who have been diagnosed with type 2 diabetes, and over forty million in our country — China which has become the second big diabetes great nation.At present type 2 diabetes treatments enable the blood sugar to achieve or to approach the normal level, take the diet treatment and the physical training as the foundation, gives the medicine treatment according to the different condition.The commonly used medicine that treat the type 2 diabetes include: Biguanide class, sulphur urea class, alpha - glucosidase inhibitor, 2,4-thiazolidinedione and insulin and so on. At present these kinds of commonly used medicines ail to have the possibility to harm the body , especially metformin which would increase the risk of the patient lactic acid acidosis. To takes orally falls the patient who the sugar medicine cannot control the blood sugar fully, often uses the insulin treatment, the insulin control blood sugar effect is good, but, often causes the hypoglycemia using the insulin treatment to occur. Therefore, needs to develop the more ideal way to control blood sugar.The glicetin -1 (glucagon-like peptide 1, GLP-1) is one kind of intestines pancreotropic hormone, GLP-1 can stimulate pancreatic island beta cell regeneration, the promotion insulin secretion, suppresses the glucagon release, reduces the speed of stomach evacuating, suppression food intake. Its insulin secretion carries on according to the blood sugar level, therefore may reduce the hypoglycemia the formation rate, Simultaneously GLP-1 also may reduce type 2 diabetes patients' body weight, is kind of brand-new diabetes medicine, Exenatide which is the analog of GLP-1 has the similar control blood sugar effect. Is suitable for type 2 diabetes patients who the oral hypoglycemic drug cannot control the blood sugar fully. After its can reduce the patient meal blood sugar and the empty stomach blood sugar effectively, to improves the saccharification hemoglobin level also to have the certain help.This experiment studies the content including below: 1. The standard Fmoc strategy solid phase synthesis of Exenatide as well as purification condition establishment. 2. The chemical constitution proof of Exenatide intermediate as well as final product. 3. Using the MTT method to measure the bioassay of Exenatide cell regeneration experiment. 4. The preliminary exploration of Convergent synthesis of Exenatide to increase the productivity.The experimental result indicated that:1. This experiment uses the standard Fmoc strategy synthesis the Exenatide molecular weight to be correct, the sequence also tallies with the peptide chain itself sequence, the amino acid ratio analysis is correct.and the racemization below 1%, therefore we can draw the conclusion that use the standard syntheticmethod to be possible to obtain Exenatide and tallies does for the drugs development as well as the bioassay requirement. 2. According to the MTT method measured the cell regeneration experiment the result also further confirmed the standard synthesis of Exenatide includes the correct amino acid sequence as well as the spatial structures. 3. Because Exenatide includes 39 amino acids to be the long peptide in the solid phase peptide synthesis field, uses the standard synthesis although may avoid questions such as racemization, but the impurity is so many that the purification condition of large-scale industrialization production is with difficulty, therefore uses the convergent synthesis to increase the productivity, furthermore uses the convergent synthesis to synthesize Exenatide not to have been reported yet. We synthesized Exenatide with convergent synthesis carry on the preliminary attempt, attempted to find the way which racemization proportion is low and fragment condensation production rate is high.