Murphy W A, Lance V A, Moreau S, Moreau J P, Coy D H
Life Sci. 1987 Jun 29;40(26):2515-22. doi: 10.1016/0024-3205(87)90073-7.
Analogs of a potent octapeptide analog of somatostatin (SRIF) H-(D)Phe-Cys-Tyr-(D)Trp-Lys-Val-Cys-Thr(NH2) were synthesized. Aromatic substitutions for Tyr resulted in little change in inhibitory potency on growth hormone (GH) secretion in the rat. Substitutions for Val or (D)Trp resulted in analogs with diminished activity. Substitution of (D)Nal for (D)Phe increased duration of GH inhibition. Final weights of subcutaneously implanted prostate tumors (R3327) were 41% lower in rats treated with an N-terminal 4-chloro-(D)phenylalanyl analog as compared to vehicle treated controls. The analog had no effect on testicular weight or final plasma testosterone levels. SRIF analogs may represent an alternative treatment for prostate cancer that would be free of the untoward reproductive effects of other treatments (e.g. LH-RH or castration).
合成了生长抑素(SRIF)的一种有效八肽类似物H-(D)苯丙氨酸-半胱氨酸-酪氨酸-(D)色氨酸-赖氨酸-缬氨酸-半胱氨酸-苏氨酸(NH2)的类似物。用芳香族氨基酸取代酪氨酸对大鼠生长激素(GH)分泌的抑制效力几乎没有影响。取代缬氨酸或(D)色氨酸得到活性降低的类似物。用(D)萘丙氨酸取代(D)苯丙氨酸可延长GH抑制的持续时间。与赋形剂处理的对照组相比,用N端4-氯-(D)苯丙氨酰类似物处理的大鼠皮下植入前列腺肿瘤(R3327)的最终重量降低了41%。该类似物对睾丸重量或最终血浆睾酮水平没有影响。SRIF类似物可能代表一种前列腺癌的替代治疗方法,它不会产生其他治疗方法(如促黄体激素释放激素或去势)的不良生殖影响。