Synthesis method and application of gram insulin
A synthesis method and technique for gram insulin, applied in the field of gram insulin, can solve problems such as chemical synthesis methods that have not yet been seen, and achieve the effects of shortening synthesis cycle, stable process and high purity
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[0027] see figure 1 , The invention provides a synthetic method of gram insulin. This synthetic method comprises the following steps:
[0028] Step S01. Provide peptide fragment 1, peptide fragment 2, peptide fragment 3, peptide fragment 4, peptide fragment 5;
[0029] Wherein, peptide fragment 1 comprises amino acids 1-11 in the main chain sequence of gram insulin and a carrier;
[0030] Peptide fragment 2 includes the 12th-24th amino acid in the main chain sequence of gram insulin and the carrier;
[0031] Peptide fragment 3 comprises amino acids at positions 25-33 in the main chain sequence of gram insulin and a carrier;
[0032] Peptide fragment 4 comprises the 34th-39th amino acid in the main chain sequence of gram insulin and the carrier;
[0033] Peptide fragment 5 comprises amino acids at positions 40-55 in the main chain sequence of gram insulin and a carrier;
[0034] Step S02. Under the action of the lysate, peptide fragment 1, peptide fragment 2, and peptide f...
Embodiment 1
[0090] A kind of synthetic method of gram insulin, its synthetic route please refer to figure 1 , including the following steps:
[0091] S11. Take 2000g (1.40mol) of resin with a degree of substitution of 0.7mmol / g, add it to the polypeptide synthesis reactor, add it to 12L DCM to swell the resin for 30min, and wash it once with DCM. Weigh 332.8g of Fmoc-Gly-OH (1.12mol) and 365.6mL of DIEA (2.08mol), dissolve them in DCM, add them to the above reactor, react for 2 hours, drain them, and wash them once with DCM. Add DCM and methanol solution with a volume ratio of 10:1, and stir to seal for 30 minutes. Drain the solvent, wash with DCM 3 times, shrink the resin 3 times with methanol, and obtain Fmoc-Gly-2-chloro-trityl resin after vacuum drying. After monitoring, the resin substitution degree is 0.45mmol / g.
[0092] Get Fmoc-Gly-2-chloro-trityl resin 560g, remove the Fmoc protecting group with a DMF solution of 20% piperidine by volume percentage, each time for 10min, twice ...
Embodiment 2
[0137] A kind of synthetic method of gram insulin, its synthetic route please refer to figure 1 , the specific process is referring to embodiment 1.
[0138] The difference between Example 2 and Example 1 is that the substitution degree of step S21 relative to Fmoc-Gly-2-chloro-trityl resin in step S11 is 0.30 mmol / g; Fmoc-Ala-2-chloro-triphenyl The substitution degree of methyl resin is 0.25mmol / g; the combination of condensing agent and activator in step S21 is DIEA / HATU, and the combination of condensing agent and activator in step S22 is DIEA / DIC.
[0139] After purification in step S210, 84.2 g of pure insulin was finally obtained, with a purity of 99.2%, a purification yield of 40.5%, and a total yield of 20.2%.
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