SU513026A1 - The method of obtaining free peptides - Google Patents

Description

(54) METHOD OF GULF ACTION OF FREE PEPTIDE

O r i m e r 3. Throyl-leucip-valn N "addemidimetyp and iinidineylngencnn,

1.7 g of carboxybenz scio-benayl-tyrosvl-leish-valvl-S-acetatidomethyl-istetin-glviina pacreopsooT ester 4,7 ml 4 and. a solution of water bromide in acetic acid, added 5a 0.31 ml of ode, kept for two days at room temperature, diluted with ether, the precipitate was filtered, dissolved in water, neuralized with 25% ammonia, the precipitate was filtered, dried and 0 was obtained 98 g (81%) of product.

Found,%: C 53.8} H 7.3; N 13.4,

 .

Calculated,%: C 54.0; H 7.05; N13.5.

Amino acid composition: tyrosine 0.93 (1), leucine 1.00 (1), valine 1.01 (1), cysteine 0.80 (1), glycine 0.98- (1).

PRI me R 4, Bis- (tyrosyl-leucylpalil) -cystinyl-bis-glycine,

To a solution of 5.0 g of bis- (carbobenzox-0-benzyl-tyrosyl-leucyl-valyl) -cystinyl-bis-glycine methyl bisodoate ester in 40 mp 4 N. solution of hydrogen bromide in acetic acid is added 2.5 ml of water and a wire t the same operations as in example 3 Obtain 2.9 g (84%) of product.

Amino acid composition: tyrosine 0.95 (1), leucine 1.00 (1), valine 0.97 (1), cysteine 0.91 (1), glycine 1.02 (1).

Example 5. Bis (asparaginyl-glutaminyl-histidyl-leucyl) -cistinip-bis-glycine.

To a solution of 2.5 g of bis- (carbobenzoxy-paraphenyl-glutaminyl-histidyl-leucyl) cystinyl-bis-glycine dimethyl ether in 8 ml of 4 N. solution of hydrogen bromide in acetic acid is added 0.5 ml of water, kept for 3 days at room temperature The solution was diluted with ether, the crystals were filtered, dissolved in water, the solution was treated with IRA-410 ion exchange resin in OH-form, evaporated, the crystals were filtered off, washed with ether, dried, and 1.87 g (90%) of product was dried.

Amino acid composition: aspartic acid 0.97 (1), glutamic acid 1.00 (1), histidine 1.05 (1), leucine, 99

(1), cystine 0.90 (1), glycine 1.10 (1). PRI me R 6. A-chain of human insulin.

. To a solution of 3.5 g of carbobenzoxy-0-benzyl-tyrosyl-glutaminyl-leucyl-tert-butyp-glutamip-asparaginyl-tyrosyl-S-a-ytamidomethylcysteinyl-asparagine methyl ester in 10 ml of 4.9 N, solution of hydrogen bromide in acetic acid 0.5 ml of water is added, the mixture is kept at room temperature for three days, diluted with ether. The precipitate is dissolved, dissolved in water, the ravine is prepared by OH exchange form in an OH-form, 2.25 g (90%) of tyrosyl are obtained. -glutaminyl-leucyl-glutam il-asparaginyl-tyrosyl-S -adamidomethyl-cysteinyl asparagine.

Amine (a liquid composition: aspartic acid. Acid 1.96 (2), glutamic acid 10 2, OO (2), leucine 1.00 (1), tyrosine 1.8 (2). Cystine 0.93 (1).

Carbobenzoxy-izoleytsil-; S Dometius -acetyl-cysteinyl-seryl-leucyl-leucyl-tirozil15 -glutaminil-glutamyl-asparaginilt tirozil- S. -atsetamidometil-aisteinil-asparagine was prepared from 1.98 g of the compound obtained above, and 0, 98 g of carbobenzoxy-isoleucyl-S-aietamido-20 methyl-cysteinyl-seryl-leucine hydrazide by the azide method. Yield 1.6 g (62%), so pl. higher than 30 (EOS, .310 (C -, dimethyl sulfoxide) Naidoy,%: C 53.00; H 6.5; N13.5 C77H, “C, 0, 3”.

2ft

Calculated,%: C 53.2; H 6.4; N 13.7.

Amino acid composition: aspartic acid 1.86 (2), glutamic acid 2.00 (2), series O, 9 (1), cystine 0.93 (1), isoleucine 0.94 (1), leucine 2.00

90 (2), tyrosine 1,7O (2).

From 1.5 g of the synthesized product and 1.0 g of carbobenzoxy-glycyl- hydrazide. isoleudylvalyl-T-tert-butyl-glutamylglutaminyl-diclo-cystynyl-threonyl-serine, the protected peptide is obtained by the azide method, which. treated successively with iodine in dimethylformamide and hydrogen bromide in trifluoroacetic acid, subjected to oxidative sulfitolysis, filtered through a column with Sefa-dex DEAZ, and 1.95 g (89%) of human insulin A-chain tetrasulfonate are obtained ((1, water).

Acnic acid composition: aspartic acid 1.92 (2), threonine 0.93 (1), serine 1.81 (2), glutamic acid 4.00 (4), glycine 1.00 (1), cystine 1.92 ( 2), valine 0.96 (1), isoleucine 1.91 (2), leucine 2.03 (2), tyrosine 1.81 (2).

The resulting product is an individual substance according to electrophoresis, with

his mobility exactly coincides with

mobility tetrasupyonat A-chain, isolated from natural insulin.

Claims (1)

Invention Formula The method of obtaining free peptide in the interaction of methyl or ethyl 513026 bb Kirbobenzoxy-Peptide Esters from the Bromine Product and Racilfea .., W with hydrogen in acetic acid, from the base, the reaction is carried out in solution b; imitating the fact that, with the aim of pure hydrogen with the addition of 4-b vol. v ,, simplify the process, increase the yield of C-water.