TH1778A - GRF analogues (GRF) - Google Patents

Abstract

A substance similar to human pancreatic GRF was synthesized to stimulate the secretion of pituitary GH in mammals. This synthetic substance is formulated as H-R1-Ala-Asp-Ala-Ile-Phe-Thr-R8-Ser-R10-Arg-R12-R13-Le u-F15-Gln-Leu-R18-Ala-Arg-Lys. -Leu-Leu-R24-R25-Ile R27-R28-Arg-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu-R38- R39-R40-Arg-R42-R43-R44-Y where R1 Or Tyr, Met, D-Tyr, Phe, D-Phe, Leu, D-Fis, or His; R8 is Ser or Asn; R10 is Tyr, Phe, or D-Tyr; R12 is Arg or Lys; R13 is Ile or Val. ; R15 is Gly or D-Ala; R18 is Tyr or Ser; R24 is His or Gln; R25 is Glu or Asp; R27 is recruited containing D and L-isomer of Ala, Nle, Ile, Leu, Met &Val; R28 is Ser, Asn or D-Ala; R34 is Arg or Ser; R38 is Gln or Arg; R39 is Arg or Gly; R40 is Ser or Ala; R42 is Phe or Ala; R43 is Asn or Arg; R44 is a natural amino acid or des-R44; And Y is the carbohydrate group of amino acids at the carbon ends, which are -COOR, -CRO, -CONHNHR, -CON (R) (R '') or -CH2OR, where R and R '' are groups. Small alkyls, tiny fluoralkyls or hydrogen, and if R is Tyr, R27 is another radical that does not use Met, R8 is Ser, R12 is Arg, R13 is Ile, R18 is Tyr, R24 is His, R25 is Glu, R28 is Asn, R34 is Arg, R38 is Gln, R39 is Arg, R40 is Ser, R42 is Phe or R43 is Asn; Peptides can also be synthesized with any radical. One or all of the 28 to 44 radicals were cut off, and the bioactive fragments were also obtained. Or prepare no salt Is the poison of this resulting peptide. In general, a peptide or piece The biologically active peptides have lengths from the nitrogen tip to the radicals between 27th and 32nd, including the non-toxic salts of these peptides. This peptide and its non-toxic salt can be used by animals. Including people and aquatic animals

Claims (1)

1. Process for fabricating substances with formula (I): H-R1-Ala-Asp-Ala-Ile-Phe-Thr-R8-Ser-R10-Arg-R12-R13- Leu-F15-Gln-Leu- R18-Ala-Arg-Lys-Leu-Leu-R24-R25-Ile R27-R28-Arg-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu-R38-R39- R40-Arg-R42-R43 -R44-Y where R1 or Tyr, Met, D-Tyr, Phe, D-Phe, Leu, D-Fis, or His; R8 is Ser or Asn; R10 is Tyr, Phe or D-Tyr; R12 is Arg or. Lys; R13 is Ile or Val; R15 is Gly or D-Ala; R18 is Tyr or Ser; R24 is His or Gln; R25 is Glu or Asp; R27 is selective group consisting of D and L-isomer of Ala. , Nle, Ile, Leu, Met, and Val; R28 is Ser, Asn, or D-Ala; R34 is Arg or Ser; R38 is Gln or Arg; R39 is Arg or Gly; R40 is Ser or Ala; R42 is Phe or Ala. ; R43 is Asn or Arg; R44 is a natural amino acid or des-R44; And Y is the amino acid carboxu group at the carbon ends, which is -COOR, -CRO, -CONHNHR, -CON (R) (R \ ') or -CH2OR, where R and R \' are groups. Small alkyls, tiny fluoralkyls or hydrogen, and if R is Tyr, R27 is another radical that does not use Met, R8 is Ser, R12 is Arg, R13 is Ile, R18 is Tyr, R24 is His, R25 is Glu, R28 is Asn, R34 is Arg, R38 is Gln, R39 is Arg, R40 is Ser, R42 is Phe or R43 is Asn; And it is also a process that prepares the tetrahydrate with any radical or both All of the 28th to 44th allowances are cut off, which will get a piece. Biologically active tabs or their non-toxic salts It consists of (a) a tepid with at least one protection group and the formula (II): X1-R1 (X X2) -Ala-Asp (X3) -Ala-Ile-Phe-Thr (X4) -. R8 (X4 X5) -Ser (X4) -R10 (X2) -Arg (X6) -R12 (X6 X7) -R13-Leu-R15-Gln (X5) -Leu-R18 (X2) -Ala-Arg (X6 ) -Lys (X7) -Leu-Leu-R24 (X or X5) -R25 (X3) -Ile-R27-R28 (X4 or X5) -Arg (X6) -Gln (X5) -Gln (X5) -Gly -Glu (X3) -R34 (X4 or X6) -Asn (X5) -Gln (X5) -Glu (X3) -R38 (X5 or X6) -R39 (X6) -R40 (X4) -Arg (X6) - R42-R43 (X5 or X6) -R44 (X8) -X9, where X, X1, X2, X3, X4, X5, X6, X7 and X8 may be hydrogen or defensive squad, and X9 may be defensive or defensive squad. The bond with the support resin, or des-X9, where the radical at the carbon end contains a carboxu group, where Y; (b) is separated from the protective group or the tiptide bond formula (II), and (c) If the resulting peptide is to be replaced in The salt is not toxic. 2. Process as mentioned. In claim 1, where X1 is hydrogen or alpha-amino protection group, X is hydrogen or His nitrogen immunity protection group; X2 is hydrogen or phenolic hydroxyl protection group. Tyr's Z; X3 is hydrogen or Asp or Glu's carboxy group; X4 is hydrogen or alcohol defensive group. The hydroxy acids of Ser and Thr; X5 is the hydrogen or shield group. Asn or Gln amino group; X6 is hydrogen or Arg guanino protection group; X7 is hydrogen or Lys lateral chain amino defense group. Claim 2 where X is Hydrogen or Tos, X1 is BOC, X2 is DCB. X3 is OBzl, X4 is Bzl, X5 is Xan, X6 is Tos, X7 is 2-chlorobenzyl coxccarbo. Nick and X8 are -NH-resin supports 4. Process, like described in one of the claims 1-3, where R1 is His 5. Same process as described in the Clause. Any of 1-4 where Y is CONH2 6. The process is the same as described in any of the claims 1-5, where R27 is Nle 7. The process is the same as described in the claim. Any of the rights from 1-6 where R10 is Tyr, R15 is Gly and R28 is Ser 8. Same process as mentioned in one of the claims from 1-6 where Tyr, R15 is D. -Ala and R28 are D-Ala 9. Process, like in one of the claims from 1-3, where R1 is D-Tyr and R27 is Nle, Val or Ile 1 0. The same goes for claim 1 in the invention of synthetic peptides with the following order: His-Ala-Asp-Ala-Ile-Phe-Thr-Ser-Ser-Tyr-Arg-Arg-Ile-Le u-Gly-Gln-Leu-Tyr-Ala-Arg-Lys-Leu-Leu-His-Glu -Ile-Met- Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Arg-Ser-Ar g-Phe-Asn 1 1.Same process as described in any of the claims from 1-10, where radicals 33 to 44 are eliminated (11 claims, 3 pages, figure).