Polypeptides having the formula:
wherein R1 is hydrogen or p-Glu; X is Glu or Asp; and R2 is NH2, Val-NH2 or Val-OH, and pharmaceutically acceptable salts have the capability of inducing the maturation of T-cell populations and thus are useful in a number of therapeutic areas.
They are prepared by classical or solid phase synthetic methods via appropriate protected peptide intermediates having the formula:
wherein R3 is R, or an a-amino protecting group, A and A1 are independently hydrogen or protecting groups for the E-amino group of lysine, B is a protecting group for the carboxyl of glutamic or aspartic acid, n is 0 or 1 and R4 is NH2 or a benzydrylamine resin support or when n is 1 R4 also represents OR5 where R5 is hydroxy, a carboxy protecting group or -CH2[polystyrene resin support] with the proviso that when R4 is amino or OH at least one of R3, A, A, and B is a protecting group. Pharmaceutical compositions are also disclosed.
具有以下式子的
多肽
其中 R1 是氢或 p-Glu;X 是 Glu 或 Asp;R2 是 NH2、Val-NH2 或 Val-OH,以及药学上可接受的盐,具有诱导 T 细胞群成熟的能力,因此可用于多个治疗领域。
它们可通过经典或固相合成方法,通过适当的受保护肽中间体制备,中间体的式为
其中 R3 是 R 或 a-
氨基保护基团,A 和 A1 分别是氢或赖
氨酸的 E-
氨基保护基团,B 是谷
氨酸或
天冬氨酸的羧基保护基团、n 是 0 或 1,R4 是 NH2 或苄基
二丙胺树脂支持物,或当 n 是 1 时,R4 还代表 OR5,其中 R5 是羟基、羧基保护基团或 -CH2[聚
苯乙烯树脂支持物],但当 R4 是
氨基或 OH 时,R3、A、A 和 B 中至少有一个是保护基团。还公开了药物组合物。