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    • 7. 发明专利
    • DK165749C
    • 1993-06-14
    • DK433684
    • 1984-09-11
    • SALK INST FOR BIOLOGICAL STUDI
    • RIVIER JEAN EDOUARD FREDERICVALE JR WYLIE WALKER
    • C12P21/00A23K1/16A61K38/00A61K38/04A61K38/18A61K38/22A61K38/25C07K14/00C07K14/575C07K14/60C07K14/61C12P21/02C07K7/10
    • Human pancreatic GRF(hpGRF), rat hypothalamic GRF(rGRF) and porcine hypothalamic GRF(pGRF) have been earlier characterized and synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which contain the sequence: R1-R2-R3-Ala-Ile-Phe-Thr-R8-Ser-R10- Arg-R12-R13- Leu-R15- Gln-R17-R18- Ala-Arg-Lys-Leu- R23-R24-R25- Ile- R27- R28- Arg-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu-R38-R39-R40-Arg-R42-R43-R44 wherein R1 is a Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His, which has either a C alpha Me or N alpha Me substitution or is unsubstituted; R2 is Ala or D-Ala; R3 is Asp or D-Asp; R8 is Ser, Asn, D-Ser or D-Asn; R10 is Tyr or D-Tyr; R12 is Arg or Lys; R13 is Ile or Val; R15 is Gly or D-Ala; R17 is Leu or D-Leu; R18 is Tyr or Ser; R23 is Leu or D-Leu; R24 is His or Gln; R25 is Glu, Asp, D-Glu or D-Asp; R27 is Met, D-Met, Ala, Nle, Ile, Leu, Nva or Val; R28 is Asn or Ser; R34 is Arg or Ser; R38 is Gln or Arg; R39 is Arg or Gly; R40 is Ser or Ala; R42 is Phe, Ala or Val; R43 is Asn or Arg; R44 is a natural amino acid; provided however that either (a) R1 has a C alpha Me or an N alpha Me substitution or (b) R17 and/or R23 is D-Leu or (c) R25 is either D-Glu or D-Asp and provided also that any or all of the residues between R29 and R44, inclusive, may be deleted; or a nontoxic salt thereof. The C-terminus is preferably amidated. These peptides as well as nontoxic salts thereof may be administered to animals, including humans and cold-blooded animals, to stimulate the release of GH and may be used diagnostically.
    • 8. 发明专利
    • FI923863A0
    • 1992-08-28
    • FI923863
    • 1992-08-28
    • SALK INST FOR BIOLOGICAL STUDI
    • RIVIER JEAN EDOUARD FREDERICVALE JR WYLIE WALKER
    • A61K38/00A61K38/35A61K38/04A61P9/12C07K14/575C07K14/655A61K
    • Analogs of CRF, which are based upon rCRF, oCRF, sauvagine and alpha-helical CRF, are disclosed that can be administered to achieve a substantial elevation of ACTH, beta -endorphin, beta -lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or an increase in blood pressure over an extended period of time. One analog which has been found to be particularly potent is: H-D-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu- Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-CM L-Nle-Glu-Ile-Ile-NH2. In the analogs of the native 41-residue polypeptides, one or more of the first six N-terminal residues may be deleted and/or the N-terminal alpha-amino group may be acylated by an acylating agent containing up to 7 carbon atoms. A number of other substitutions may also be made throughout the chain. These analogs or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans. These analogs may also be used as stimulants to elevate mood and improve memory and learning, as well as diagnostically.
    • 9. 发明专利
    • NO168043B
    • 1991-09-30
    • NO851947
    • 1985-05-15
    • SALK INST FOR BIOLOGICAL STUDI
    • VALE JR WYLIE WALKERRIVIER JEAN EDOUARD FREDERIC
    • C07K14/575A23K1/16A61K38/00A61K38/04A61K38/18A61K38/22A61K38/25A61P5/00C07K14/00C07K14/60C07K14/61G01N33/68C07K7/10
    • Human GRF(hGRF), rat GRF(rGRF), porcine GRF(pGRF) and bovine GRF(bGRF) have been earlier characterized and synthetized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which have the sequence: R1-R2-R3-Ala-Ile-Phe-Thr-R8-Ser-R10-Arg-R12-R13-R14-R15-Gln-R17-R18-Al a-Arg-Lys-Le u-R23-R24-R25-Ile-R27-R28-R29-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu-R38-R39- R40-Arg-R42- R43-R44 wherein R1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Lou, His or D-His having either a C Me or N Me substitution or being unsubstituted; R2 is Ala, D-Ala or D-NMA; R3 is Asp or D-Asp; R8 is Ser, Asn, D-Ser or D-Asn; R10 is Tyr or D-Tyr; R12 is Arg or Lys; R13 is Ile or Val; R14 is Leu or D-Leu; R15 is Gly or D-Ala; R17 is Leu or D-Leu; R18 is Tyr or Ser; R23 is Leu or D-Leu; R24 is His or Gln; R25 is Glu, Asp, D-Glu or D-Asp; R27 is Met, D-Met, Ala, Nle, Ile, Leu, Nva or Val; R28 is Asn or Ser; R29 is Arg or D-Arg; R34 is Arg or Ser; R34 is Gln or Arg; R39 is Arg or Gly; R40 is Ser or Ala; R42 is Phe, Ala or Val; R43 is Asn or Arg; R44 is a natural amino acid; provided however that any or all of the residues between R28 and R44, inclusive, may be deleted and provided also that R2 is D-NMA and/or R14 is D-Leu and/or R29 in is D-Arg. Those peptides as well as their nontoxic salts may also be used diagnostically.
    • 10. 发明专利
    • FI906240A0
    • 1990-12-18
    • FI906240
    • 1990-12-18
    • SALK INST FOR BIOLOGICAL STUDI
    • RIVIER JEAN EDOUARD FREDERICVALE JR WYLIE WALKERRIVIER CATHERINE LAURE
    • A61K38/04A61K38/00A61P5/00C07K14/575C07K14/60C07K
    • The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans and also resist enzymatic degradation in the body. The peptides have the sequence: (B)R1-R2-R3-Ala-(Q1)R5-Phe-Thr-R8-Ser(Q2)R10-Arg-R12-(Q3)R13-Leu-R15-G ln-(Q4)Leu-R18-(Q5)Ala-Arg-R21-(Q6)R22-(Q7)Leu-R24-R25-(Q8)R26-(Q9)R27 -R28-Arg-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu-R38-R39-R40-Arg-R42-R43-R44 wherein R1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His; B is H, CaMe, NaMe, desamino, Ac or For; R2 is Ala, D-Ala, NMA or D-NMA; R3 is Asp or D-Asp; R5 is Ile or Leu; R8 is Ser, Asn, Lys, Arg, Asp or Glu; R10 is Tyr, D-Tyr or Phe; R12 is Arg or Lys; R13 is Ile, Val, Leu or Ala; R15 is Gly or Ala; R18 is Ser or Tyr; R21 is Lys, D-Lys, Arg or D-Arg; R22 is Leu, Ile, Ala or Val; R24 is Gln or His; R25 is Asp or Glu; R26 is Ile or Leu; R27 is Met, D-Met, Ala, Nle, Ile, Leu, Nva or Val; R28 is Asn or Ser; R34 is Ser or Arg; R38 is Arg or Gln; R39 is Gly or Arg; R40 is Ala or Ser; R42 is Phe, Ala or Val; R43 is Asn or Arg; R44 is a natural amino acid; Q1-Q9 are either H or CaMe, provided however that one of Q1-Q9 is CaMe. These peptides may also be used diagnostically, and the C-terminus can be shortened to residue-29.