Long-acting glucagon-like peptide-1 analog dimer and its medical application
A technology of glucagon and analogues, applied in medicine, in the field of dimer of glucagon-like peptide-1 analogues, can solve problems such as medication compliance that needs to be improved
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Embodiment 1
[0063] A. Preparation of GLP-1 analogue monomer:
[0064] 1) Synthesis: Fmoc method is adopted, and the step-by-step synthesis method is implemented according to the following steps:
[0065] a) Fmoc-arginine-resin is obtained by coupling an amino resin solid-phase support and Fmoc-protected arginine in the presence of an activator system;
[0066] b) Connect amino acids in accordance with the amino acid sequence of the peptide sequence by solid-phase synthesis to obtain a peptide-resin conjugate with N-terminal Fmoc-protection and side chain protection; take the following protection measures for amino acids with side chains: use Boc (tert. Butoxycarbonyl), OtBu (oxygen-tert-butyl) for glutamic acid, Boc (tert-butoxycarbonyl) for lysine, Trt (trityl) for glutamine, tBu (tert-butyl) for tyrosine ), Trt (trityl) or tBu (tert-butyl) for serine, OtBu (oxygen-tert-butyl) for aspartic acid, tBu (tert-butyl) for threonine, and Trt (three-butyl) for histidine benzyl) or Boc (tert-bu...
Embodiment 2
[0079] A. Preparation of GLP-1 analogue monomer:
[0080] 1) Synthesis: Fmoc method is adopted, and the step-by-step synthesis method is implemented according to the following steps:
[0081] a) In the presence of an activator system, Fmoc-Gly-resin is obtained by coupling an amino resin solid-phase support and Fmoc-protected glycine;
[0082] b) Connect amino acids in accordance with the amino acid sequence of the peptide sequence by solid-phase synthesis to obtain a peptide-resin conjugate with N-terminal Fmoc-protection and side chain protection; take the following protection measures for amino acids with side chains: use Boc (tert. Butoxycarbonyl), OtBu (oxygen-tert-butyl) for glutamic acid, Boc (tert-butoxycarbonyl) for lysine, Trt (trityl) for glutamine, tBu (tert-butyl) for tyrosine ), Trt (trityl) or tBu (tert-butyl) for serine, OtBu (oxygen-tert-butyl) for aspartic acid, tBu (tert-butyl) for threonine, and Trt (three-butyl) for histidine benzyl) or Boc (tert-butoxyc...
Embodiment 3
[0095] A. Preparation of GLP-1 analogue monomer:
[0096] 1) Synthesis: Fmoc method is adopted, and the step-by-step synthesis method is implemented according to the following steps:
[0097] a) Fmoc-Ala-resin is obtained by coupling a resin solid phase support and Fmoc-protected alanine in the presence of an activator system;
[0098] b) Connect amino acids in accordance with the amino acid sequence of the peptide sequence by solid-phase synthesis to obtain a peptide-resin conjugate with N-terminal Fmoc-protection and side chain protection; take the following protection measures for amino acids with side chains: use Boc (tert. Butoxycarbonyl), OtBu (oxygen-tert-butyl) for glutamic acid, Boc (tert-butoxycarbonyl) for lysine, Trt (trityl) for glutamine, tBu (tert-butyl) for tyrosine ), Trt (trityl) or tBu (tert-butyl) for serine, OtBu (oxygen-tert-butyl) for aspartic acid, tBu (tert-butyl) for threonine, and Trt (three-butyl) for histidine benzyl) or Boc (tert-butoxycarbonyl)...
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