技术特征：
1.一种多肽化合物，其特征在于，所述多肽化合物具有以下氨基酸序列表示的母体肽：h-xaa
1-xaa
2-glu
3-gly
4-xaa
5-phe
6-xaa
7-xaa
8-asp
9-val
10-xaa
11-ser
12-xaa
13-leu
14-glu
15-gly
16-gln
17-xaa
18-ala
19-xaa
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-xaa
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2；其中，xaa1＝his或d-his或ac-his；xaa2＝ala或aib或d-ala或nmeala；xaa5＝thr或d-thr或thr(o-phospho)或thr(o-β-d-glucose)；xaa7＝thr或d-thr或thr(o-phospho)或thr(o-β-d-glucose)；xaa8＝ser或d-ser或ser(o-phospho)或ser(o-β-d-glucose)；xaa
11
＝ser或d-ser或ser(o-phospho或ser(o-β-d-glucose)；xaa
13
＝tyr或d-tyr或tyr(o-phospho)或tyr(o-β-d-glucose)；xaa
18
＝ala或aib或d-ala或nmeala；xaa
20
＝lys(oct-γglu-aeea-aeea)或lys(pal-γglu-aeea-aeea)或lys(c16-γglu-aeea-aeea)或lys(c20-γglu-aeea-aeea)或lys(c22-γglu-aeea-aeea)或lys(peg-γglu-aeea-aeea)或orn(oct-γglu-aeea-aeea)或dap(oct-γglu-aeea-aeea)或dab(oct-γglu-aeea-aeea)或lys(biotin)或cys(maleimide)或cys(maleimide-oct-γglu-aeea-aeea)或cys(maleimide-pal-γglu-aeea-aeea或cys(maleimide-c20-γglu-aeea-aeea)；xaa
28
＝lys或arg或d-arg。2.根据权利要求1所述的多肽化合物，其特征在于，所述多肽化合物为asp
9-lys
32
侧链酰胺键环肽，glu
3-lys
32
侧链酰胺键环肽或glu
15-lys
32
侧链酰胺键环肽。3.根据权利要求1所述的多肽化合物，其特征在于，所述多肽化合物具有如下之一氨基酸序列表示的母体肽，analog1：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog2：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(pal-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog3：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(c16-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog4：
glu
15-gly
16-gln
17-ala
18-ala
19-cys(maleimide-pal-oct-γglu-aeea-aeea))
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog13：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-cys(maleimide-c20-oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog14：h-his
1-ala
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog15：h-his
1-aib
2-glu
3-gly
4-d-thr
5-phe
6-d-thr
7-d-ser
8-asp
9-val
10-d-ser
11-d-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog16：h-his
1-d-ala
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog17：h-his
1-nmeala
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog18：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-aib
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-d-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog19：h-his
1-d-ala
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-d-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-d-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog20：
analog28：d-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-d-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2analog29：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2(asp
9-lys
32
酰胺键环肽)analog30：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2(glu
3-lys
32
酰胺键环肽)analog31：h-his
1-aib
2-glu
3-gly
4-thr
5-phe
6-thr
7-ser
8-asp
9-val
10-ser
11-ser
12-tyr
13-leu
14-glu
15-gly
16-gln
17-ala
18-ala
19-lys(oct-γglu-aeea-aeea)
20-glu
21-phe
22-ile
23-ala
24-trp
25-leu
26-val
27-arg
28-gly
29-arg
30-gly
31-lys
32-arg
33-asn
34-arg
35-asn
36-asn
37-ile
38-ala
39-nh2(glu
15-lys
32
酰胺键环肽)。4.权利要求1-3任一项所述的多肽化合物作为glp-1r/gcgr/gipr三重受体激动剂的应用。5.权利要求1-3任一项所述的多肽化合物作为预防和/或治疗代谢性疾病药物的应用。6.一种预防和/或治疗代谢性疾病的药物组合物，其特征在于，所述药物组合物包括权利要求1-3任一项所述的多肽化合物或其组合物。7.根据权利要求6所述的药物组合物，其特征在于，所述代谢性疾病包括糖尿病、高血糖、肥胖症、高脂血症、动脉硬化、脂肪肝和/或糖尿病并发症。8.根据根据权利要求7所述的应用，其特征在于，所述脂肪肝为非酒精性脂肪肝；所述非酒精性脂肪肝包括非酒精性脂肪样变性、非酒精性脂肪肝炎、肝纤维化和/或肝纤维化合并的肝硬化；所述糖尿病并发症包括糖尿病肾病、糖尿病高血压、糖尿病眼疾和/或糖尿病神经性病变。
技术总结
本发明公开一种GLP-1R/GCGR/GIPR三重受体激动剂及其应用。本发明提供的一种多肽化合物具有以下氨基酸序列表示的母体肽：H-Xaa
技术研发人员：王宇恩 张凌云 戴政清 马亚平
受保护的技术使用者：深圳深创生物药业有限公司
技术研发日：2022.01.25
技术公布日：2022/5/6