首页> 外国专利> Glucagon-like peptide-2 (GLP-2) analogs for the treatment of bowl disorders resistant to dipeptidyl peptidase IV (DPP-IV) digestion

Glucagon-like peptide-2 (GLP-2) analogs for the treatment of bowl disorders resistant to dipeptidyl peptidase IV (DPP-IV) digestion

机译:胰高血糖素样肽2(GLP-2)类似物,用于治疗对二肽基肽酶IV(DPP-IV)消化有抵抗力的碗疾病

摘要

Analogs of glucagon-like peptide-2 (GLP-2), a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical and therapeutic use in treating disorders of the small bowel is described. The GLP-2 analog is characterised by intestinotrophic activity and which conforms to formula described below: R1-(Y1)m-X1-X2-X3-X4-Ser5, Phe6-Ser7-Asp8-(P1)-Leu14-Asp15-Asn16-Leu17-Ala18-X19-X20-Asp21-Phe22-(P2)-Trp25-Leu26-Ile27-Gln-28-Thr29-Lys30-(P3)-(Y2)n-R2 Wherein X1 is His or Tyr X2 is Ala or an Ala-replacement amino acid conferring on said analog resistance to DPP-IV enzyme X3 is Pro, HPro, Asp or Glu X4 is Gly or Ala P1 is Glu-X10-Asn-Thr-Ile or Tyr-Ser-Lys-Tyr X10 is Met or an oxidatively stable Met-replacement amino acid X19 is Ala or Thr X20 is Arg, Lys, His or Ala P2 is Ile-Asn, Ile-Ala or Val-Gln P3 is a covalent bond, or is Ile, Ile-Thr or Ile-Thr-Asp R1 is H or an N-terminal blocking group R2 is OH or a C-terminal blocking group Y1 is one or two basic amino acids selected from the group Arg, Lys and His Y2 is one or two basic amino acids selected from the group Arg, Lys and His m and n, independently, are 0 or 1 and wherein at least one of X1, X2, X3, X4, P1, X10, X19, X20, P2 and P3 is other than a wild type, mammalian GLP-2 residue
机译:胰高血糖素基因表达产物胰高血糖素样肽2(GLP-2)的类似物已被确定为肠道组织生长因子。描述了它们作为治疗小肠疾病的药物和治疗用途的制剂。 GLP-2类似物的特征是肠道营养活性,并符合以下所述的通式:R1-(Y1)m-X1-X2-X3-X4-Ser5,Phe6-Ser7-Asp8-(P1)-Leu14-Asp15-Asn16 -Leu17-Ala18-X19-X20-Asp21-Ph​​e22-(P2)-Trp25-Leu26-Ile27-Gln-28-Thr29-Lys30-(P3)-(Y2)n-R2其中X1为His或Tyr X2为Ala或赋予所述对DPP-IV酶X3类似物抗性的Ala取代氨基酸是Pro,HPro,Asp或Glu X4是Gly或Ala P1是Glu-X10-Asn-Thr-Ile或Tyr-Ser-Lys-Tyr X10是Met或氧化稳定的Met置换氨基酸X19是Ala或Thr X20是Arg,Lys,His或Ala P2是Ile-Asn,Ile-Ala或Val-Gln P3是共价键,或者是Ile,Ile -Thr或Ile-Thr-Asp R1为H或N末端封闭基团R2为OH或C末端封闭基团Y1为选自Arg,Lys和His Y2组的一个或两个碱性氨基酸选自组Arg,Lys以及His m和n的碱性氨基酸分别为0或1,并且其中X1,X2,X3,X4,P1,X10,X19中的至少一个, X20,P2和P3不是野生型哺乳动物GLP-2残基

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