TH2482B - GRF analogues (GRF) - Google Patents

Abstract

A metabolite similar to human pancreatic GRF was synthesized to induce pituitary GH secretion in mammals. This synthetic has the following formula: 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 selectively composed of D and L-isomers 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 carboxy group of amino acids at the carbon end, which is -COOR, -CRO, -CONHNHR, -CON(R)(R'') or -CH2OR, where R and R'' are groups. small alkyl small fluoroalkyl or hydrogen and if R is Tyr, R27 is a non-Met radical, 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; It can also synthesize peptides with any oxidant. One or all of the radicals 28 to 44 were eliminated and bioactive fragments were obtained. or prepare a salt that is not The toxicity of this peptide generally peptides or fragments The length of these biologically active peptides from the nitrogen tip to the radical between the 27th and 32nd order includes the innocuous 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. 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 sequence: 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, with radicals 33 to 44 eliminated (11 claims, 3 pages, figure)