GB992958A - Polypeptides and process for their manufacture - Google Patents

Polypeptides and process for their manufacture

Info

Publication number
GB992958A
GB992958A GB2751461A GB2751461A GB992958A GB 992958 A GB992958 A GB 992958A GB 2751461 A GB2751461 A GB 2751461A GB 2751461 A GB2751461 A GB 2751461A GB 992958 A GB992958 A GB 992958A
Authority
GB
United Kingdom
Prior art keywords
arginyl
ester
tert
lysyl
butyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB2751461A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF Schweiz AG
Original Assignee
Ciba AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CH865860A external-priority patent/CH427842A/en
Application filed by Ciba AG filed Critical Ciba AG
Publication of GB992958A publication Critical patent/GB992958A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/665Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
    • C07K14/68Melanocyte-stimulating hormone [MSH]

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The invention comprises peptides of the formula L - seryl - L - tyrosyl - L - seryl - L-(X) - L - glutaminyl - L - histidyl - L - phenylalanyl - L - arginyl - L - tryptopyl - glycyl-L - lipyl - L - prolyl - L - valyl - glycyl - L - lipyl - L - lysyl - L - arginyl - L - arginyl - L - pioline in which X represents an acyl residue derived from an unsubstituted or a mercapto substituted, a C1-2-alkylmercapto, a sulphoxy-substituted or a sulpho-substituted a -C1-4-alkyl-a -aminoacetic acid and the peptides where the L-glutaminyl residue is replaced by the L-glutamyl residue, the esters, amides, hydrazides, N-acyl and amino protected derivatives and the acid addition salts thereof and a process for their preparation wherein the amino-acids L-serine, L-tyrosine, L-serine, L-(X)-OH, L-glutamine or L-glutamic acid, L-histidine, L-phenylalanine, L-arginine, L-tryptophane, glycine, L-lysine, L-proline, L-valine, glycine L-lysine, L-lysine, L-arginine, L-arginine, L-proline are linked together in the indicated order of succession by (a) reaction, in the presence of a condensing agent, of an amino acid molecule or peptide molecule in the form of an ester having a free amino group with another amino acid molecule or peptide molecule containing a protected amino group, or (b) reaction of an amino-acid ester or peptide ester having a free amino group with an amino acid or a peptide having an activated carboxyl group and a protected amino group, or (c) reaction of an amino acid or a peptide having a free carboxyl group and a protected amino group with an amino acid or a peptide having an activated amino group and a protected carboxyl group; and pharmaceutical compositions containing the polypeptides. The residue X is preferably alanyl, valyl, leucyl, isoleucyl, a -aminobutyryl, cysteinyl, or methionyl or its sulphoxide or sulphone. In the process it is preferred to form the nonadecapeptide either by condensing a deca- and a nona-peptide or tetra- and a penta-decapeptide. Na - Trityl - Ne - tertiarybutyloxycarbonyl-L-lysyl - L - prolyl - L - valyl - glycine ethyl ester is prepared by tritylating the free amino peptide. This compound is hydrolysed to the free acid and converted into Na -trityl-Ne -tertiarybutyloxycarbonyl - L - lysyl - L - prolyl-L - valyl - glycyl - (Ne - tertiary - butoxy carbonyl)-L - lysyl - (Ne - tertiary - butyloxy carbonyl)-L - lysyl - nitro - L - arginyl - nitro - L - arginyl-L - proline tertiary butyl ester, and its free acid. The nonapeptide ester is selectively detritylated to the free amino peptide and the nitro groups reduced to give Ne - tertiarybutyloxycarbonyl - L - lysyl - L - prolyl - L - valyl-glycyl - (Ne - tertiarybutyloxycarbonyl) - L-lysly (Ne - tertiarybutyloxycarbonyl) - L - lysyl - L - arginyl - L - arginyl - L - proline tertiary butyl ester acetate and tritosylate salts. The last-named nonapeptide is also prepared through either the Na -(p-phenylazo-benzyloxycarbonyl)-or Na -carbobenzyloxycarbonyl-nonapeptides in turn prepared by condensation of the appropriate tetra- and pentapeptides. Na - carbobenzyloxy - Ne - tertiary-butyloxycarbonyl - L - lysyl - L - prolyl - L - valyl - glycine is prepared from L-prolyl-L-valyl-glycine ethyl ester and the blocked L-lysine to give the tetrapeptide ethyl ester which is hydrolysed. Ne - Tertiary-butyloxycarbonyl - L-lysine is prepared from L-lysine and either tertiarybutyl-phenyl carbonate or tertiary-butyl-p-nitraphenyl carbonate in the presence of "Amberlite" XE-64 (Registered Trade Mark) and is carbobenzoxylated to give the Na carbobenzyloxy - Ne - tertiary - butylcarbonyl-L - lysine. Carbobenzoxy - L - glutamic acid-a -benzyl ester and iso butylene gave carbobenzoxy - a - benzyl - g - tert - butyl ester and this on hydrolysis gave carbobenzoxy-g -tert-butyl ester which was purified through the dicyclohexylamine salt. Similarly is prepared the a - ethyl - g - tert - butyl ester. The carbobenzoxy-g -tert-butyl ester was reacted with histidine methyl ester to give carbobenzoxy-(g -tert-butyl)-L - glutamyl - L - histadine methyl ester and then the free acid. The ester is also converted into the hydrazide. The free acid or the azide (prepared from the hydrazide) is condensed with L - phenylalanyl - nitro - L arginyl - L - tryptophyl-glycine methyl ester to give carbobenzoxy-(g - tert - butyl) - L - glutamyl - L - histidyl - L-phenylalanyl - nitro - L - arginyl - L - tryptophylglycine methyl ester and the free acid and g - tert - butyl - L - glutamyl - L - histidyl - L-phenylalanyl - L - arginyl - L - tryptophylglycine. The new foregoing hexapeptide and the nonapeptide were condened to give g -tert-butyl - L - glutamyl - L - hisitidyl - L - phenylalanyl - L - arginyl - L - tryptophyl - glycyl - (Ne -tert - butyl - oxycarbonyl) - L - lysyl - L - prolyl-L - valyl - glycyl - (Ne - tert - butyloxycarbonyl)-L - lysyl - (Ne - tert - butyloxycarbonyl) - L-lysyl - L - arginyl - L - arginyl - L - proline-tert butyl ester, through the Na -carbobenzyloxy derivative. Pharmaceutical compositions having MSH action comprise the nonadecapeptides of the invention in conjunction with or in admixture with a pharmaceutically suitable carrier. The compositions may be in the form of tablets, dragees, ampoules, vials, powders, ointments, creams, suppositories, solutions, suspensions or emulsions, which may contain other therapeutically useful substances. Specifications 872,332, 895,345, 957,892 and 992,957 are referred to.
GB2751461A 1960-07-29 1961-07-28 Polypeptides and process for their manufacture Expired GB992958A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH865860A CH427842A (en) 1960-07-29 1960-07-29 Process for the production of new polypeptides
CH1188260 1960-10-24
CH1290360 1960-11-17
CH1364160 1960-12-06

Publications (1)

Publication Number Publication Date
GB992958A true GB992958A (en) 1965-05-26

Family

ID=27429168

Family Applications (1)

Application Number Title Priority Date Filing Date
GB2751461A Expired GB992958A (en) 1960-07-29 1961-07-28 Polypeptides and process for their manufacture

Country Status (1)

Country Link
GB (1) GB992958A (en)

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