申请人:The Administrators of
The Tulane Educational Fund
公开号:EP0277626A2
公开(公告)日:1988-08-10
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 have the sequence:
Q¹-CO-R₂-R₃-Ala₄-Ile₅-Phe₆-Thr₇-R₈-Ser₉-R₁₀-Arg₁₁-R₁₂-R₁₃-R₁₄-R₁₅-Gln₁₆-R₁₇-R₁₈-Ala₁₉-Arg₂₀-Lys₂₁-Leu₂₂-R₂₃-R₂₄-R₂₅-Ile₂₆-R₂₇- R₂₈-NH-Q²
wherein Q¹ is an omega or alpha-omega substituted alkyl,
Q² is a lower omega-guanidino-alkyl group.
R₂ is Ala,D-Ala,or D-N-Methyl-Ala
R₃ is Asp,D-Asp,Glu,or D-Glu
R₈ is Asn,D-Asn,Ser, or D-Ser
R₁₀ is Tyr or D-Tyr
R₁₂ is Lys, D-Lys Arg or Orn
R₁₃ is Val or Ile
R₁₄ is Leu or D-Leu
R₁₅ is Gly,N-Methyl-Gly, or D-Ala
R₁₇ is Leu or D-Leu
R₁₈ is Tyr or Ser
R₂₃ is Leu or D-Leu
R₂₄ is Gln or His
R₂₅ is Asp,D-Asp,Glu, or D-Glu
R₂₇ is Met,D-Met,Ala,Nle,Ile,Val,Nva,Leu
R₂₈ is Asn or Ser
The 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.
人胰腺促肾上腺皮质激素(hpGRF)、大鼠下丘脑促肾上腺皮质激素(rGRF)和猪下丘脑促肾上腺皮质激素(pGRF)早先已被表征和合成。本发明提供的合成肽在刺激包括人在内的动物释放垂体促肾上腺皮质激素方面具有极强的效力,在体内具有抗酶降解的能力,其序列如下:
Q¹-CO-R₂-R₃-Ala₄-Ile₅-Phe₆-Thr₇-R₈-Ser₉-R₁₀-Arg₁₁-R₁₂-R₁₃-R₁₄-R₁₅-Gln₁₆-R₁₇-R₁₈-Ala₁₉-Arg₂₀-Leu₂₁-Leu₂₂-R₂₃-R₂₄-R₂₅-Ile₂₆-R₂₇- R₂₈-NH-Q²
其中 Q¹ 是欧米茄或α-欧米茄取代烷基、
Q² 是低级欧米伽胍基烷基。
R₂ 是 Ala、D-Ala 或 D-N-Methyl-Ala
R₃ 是 Asp、D-Asp、Glu 或 D-Glu
R₈ 是 Asn、D-Asn、Ser 或 D-Ser
R₁₀ 是 Tyr 或 D-Tyr
R₁₂ 是 Lys、D-Lys Arg 或 Orn
R₁₃ 是 Val 或 Ile
R₁₄ 是 Leu 或 D-Leu
R₁₅ 是 Gly、N-甲基-Gly 或 D-Ala
R₁₇ 是亮氨或 D-亮氨
R₁₈ 是 Tyr 或 Ser
R₂₃ 是 Leu 或 D-Leu
R₂₄ 是 Gln 或 His
R₂₅ 是 Asp、D-Asp、Glu 或 D-Glu
R₂₇ 是 Met、D-Met、Ala、Nle、Ile、Val、Nva、Leu
R₂₈ 是 Asn 或 Ser
这些肽及其无毒盐可用于动物,包括人类和冷血动物,以刺激 GH 的释放,也可用于诊断。