Study On The Synthesis Process Of Peptide Drugs—Thymosin ?1 And Salmon Calcitonin

Thymosin ?1(also known as Talpha 1 or Thymalfasin),a 28 amino acid polypeptide active drug,is produced by prothymosin after peptidase cleavage asparagine within the form,and mainly exists in the thymus.Thymosin al plays an important role ihepatitis C and immuno deficiency diseases in clinic.The manufacturing methods of synthetic n regulating immune,endocrine and central nervous system.Thymosin al has been used for the treatment of chronic hepatitis B,Thymosin al mainly include solution phase synthesis,gene recombinant and full solid phase peptide synthesis.In this dissertation,a combination of both solution-and solid-phase peptide synthesis employed in the synthesis of Thymosin al.We divided 28 amino acids sequence into several segments.firstly,we synthetize each fully protected fragment using the solid phase synthesis method,and then coupled each fully protected fragment together in the solution phase,so that forming a full protection Thymosin al crude peptide.After cleaved Thymosin al crude peptide,crude peptide was further purified by reversed phase high-performance liquid chromatography(RP-HPLC).Finally we obtained pure Thymosin al.Convergent peptide synthesis can successffully avoid the problems that it is difficult and incomplete to condensation after twelve amino acid coupled,while easy to forming the p-structure in SPPS.Futher more,it also has the following advantages,including low cost,high yield of crude peptide and high purity of the crude peptide.Futher more,it also has the following advantages,including low cost,high yield and high purity of crude peptide,and very suitability for industrial production.Salmon calcitonin is a biologically active peptide consisting of 32 amino acids,between the N-terminal first and seventh amino acid form a pair of two disulfide,C-terminal is amide bond.Clinical is used mainly for the long-term therapy of osteoporosis.At present,synthesis of salmon calcitonin is focused on gene recombination and full solid phase synthesis.In this dissertation,we first synthetize calcitonin salmon by solid-liquid combined manner.Primarily,we divided 32 amino acid sequence into 3 or 4 peptide fragments in the whole experiment,and then we synthetize these fully protected peptide fragments in SPPS.Further,we coupled up these fully protected peptide fragments in the liquid phase,so as to obtain the full protection Salmon calcitonin crude peptide,after cleaved and HPLC purification,finally we get the Salmon calcitonin pure peptide.We synthetize Salmon calcitonin by this approach,It enhances yield and purity of peptide,and is conducive to large-scale production.