The invention relates to novel peptides and peptide derivatives which act as antagonists of natural LH-RH and have the general formula:
X-R1-R2-R3-Ser-Tyr-R4-R5-R6-R7-R8-NH2 wherein
X represents hydrogen or a lower acyl (1-6 C) group,
R' and R2 represent either the same or different groups selected from D-Bal (2), D-Bal (3), D-Nal (1), D-Nal (2), D-Phe or D-Phe substituted at the phenyl moiety by one or more halogen, alkyl (1-4 C), alkoxy (1- 4 C) or nitro groups; R' represents D-Trp, D-Bal (2), D-Bal (3), D-Nal (1), D- Nal (2) or D-Pal, with the proviso that at least one of the symbols R' or R3 represents a D-Bal (2) or D-Bal (3) group;
R4 represents D-Arg, D-Lys, D-homo Arg or D-dialkyl (1-4 C)-homo Arg;
R5 represents L-Leu, L-Met or the alkyl (1-4C) or phenylalkyl
(7-10C) ether of L-Cys, L-Ser or L-homo Ser;
R6 represents L-Lys or L-Arg;
R7 represents L-Pro or L-thiaprolyl, and
R8 represents D-Ala or Gly.
The invention also includes the acid addition salts of the above defined peptides.
本发明涉及可作为天然 LH-RH 拮抗剂的新型肽和肽衍
生物,其通式为
X-R1-R2-R3-Ser-Tyr-R4-R5-R6-R7-R8-NH2 wherein
X 代表氢或低级酰基(1-6 C)、
R' 和 R2 代表相同或不同的基团,选自 D-Bal(2)、D-Bal(3)、D-Nal(1)、 D-Nal(2)、D-Phe 或在苯基被一个或多个卤素、烷基(1-4 C)、烷氧基(1-4 C)或硝基取代的 D-Phe;R' 代表 D-Trp、D-Bal (2)、D-Bal (3)、D-Nal (1)、D-Nal (2) 或 D-Pal,但 R' 或 R3 中至少有一个符号代表 D-Bal (2) 或 D-Bal (3) 基团;
R4 代表 D-Arg、D-Lys、D-高分子 Arg 或 D-二烷基(1-4 C)-高分子 Arg;
R5 代表 L-Leu、L-Met 或其烷基(1-4C)或苯基烷基(7-10C)醚。
(L-Cys、L-Ser 或 L-homo Ser 的烷基(1-4C)或苯基烷基(7-10C)醚;
R6 代表 L-Lys 或 L-Arg
R7 代表 L-Pro 或 L-巯基,以及
R8 代表 D-Ala 或 Gly。
本发明还包括上述定义的肽的酸加成盐。