CN1268640C - 胰高血糖素样肽-2的类似物 - Google Patents
胰高血糖素样肽-2的类似物 Download PDFInfo
- Publication number
- CN1268640C CN1268640C CNB971953317A CN97195331A CN1268640C CN 1268640 C CN1268640 C CN 1268640C CN B971953317 A CNB971953317 A CN B971953317A CN 97195331 A CN97195331 A CN 97195331A CN 1268640 C CN1268640 C CN 1268640C
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- Prior art keywords
- hglp
- analogue
- glp
- ala
- gly
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- 238000006386 neutralization reaction Methods 0.000 description 1
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- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Pharmacology & Pharmacy (AREA)
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- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
# | GLP-2类似物(除注明外,均为1-33) | 小肠重量增加% |
1 | rGLP-2 | 45 |
2 | [Tyr1]rGLP-2 | 37 |
3 | [D-Ala2]rGLP-2 | 86 |
4 | [Gly2]rGLP-2 | 70 |
5 | [Val2]rGLP-2 | 65 |
6 | [Gly2]hGLP-2 | 59 |
7 | [Gly2Ala20]hGLP-2 | 46 |
8 | [Gly2Ala10]hGLP-2 | 33 |
9 | [Ala1Gly2]hGLP-2 | 23 |
10 | [Gly2Ala3]hGLP-2 | 18 |
11 | [Gly2Ala4]hGLP-2 | 36 |
12 | [Glu3]rGLP-2 | 33 |
13 | [Ala4]rGLP-2 | 30 |
14 | [Tyr9Ser10Lys11Tyr12(desIle13)]hGLP-2 | 41 |
15 | [Leu10]rGLP-2 | 26 |
16 | [Nleu10]rGLP-2 | 52 |
17 | [MerSO2 10]rGLP-2 | 8 |
18 | [Lys20]rGLP-2 | 62 |
19 | [Val23Gln24]hGLP-2 | 36 |
20 | 酰胺化C端 | 23 |
21 | [Gly2Ala24]hGLP-2 | 67 |
22 | [Gly2Ala8]hGLP-2 | 33 |
23 | [Gly2Ala11]hGLP-2 | 42 |
24 | [Gly2Ala21]hGLP-2 | 35 |
25 | [Gly2Ala9]hGLP-2 | 31 |
26 | [Gly2Ala16]hGLP-2 | 36 |
27 | [Gly2Ala17]hGLP-2 | 36 |
28 | [Gly2Ala28]hGLP-2 | 31 |
29 | [Gly2Ala5]hGLP-2 | 38 |
30 | [Gly2Ala31]hGLP-2 | 28 |
31 | [Gly2Ala27]hGLP-2 | 22 |
32 | [Gly2Ala12]hGLP-2 | 18 |
33 | [Gly2Ala13]hGLP-2 | 18 |
34 | [Gly2Ala7]hGLP-2 | 22 |
35 | [Gly2Ala6]hGLP-2 | 18 |
鉴定 | 序列描述ALE-0109 | 相对于rGLP-2的活性% | DPP-IV切割的百分比 |
大鼠GLP-2(1-33) | 天然大鼠序列 | 100% | 58% |
大鼠GLP-2(4-33) | N-3;除去3个N端残基 | 6% | |
Ac-大鼠GLP-2(1-33) | N-乙酰基 | 44% | 0% |
琵琶鱼GLP-1 | 天然琵琶鱼GLP-1 | 7% | |
[Arg-1]大鼠GLP-2(1-33) | Arg加入N端 | 11% | 0% |
大鼠GLP-2(1-30) | C-3;除去3个C端残基 | 23% | |
大鼠GLP-2(1-25) | C-8;除去8个C端残基 | 8% | |
大鼠GLP-2(1-33)酰胺 | C端酰胺 | 56% | |
[Arg-2,Arg-1]大鼠GLP-2(2-33) | Arg-Arg加入N端 | 43% | 0% |
[DAla2]大鼠GLP-2(1-33) | Ala2->D-Ala2 | 210% | 0% |
[Gly2]大鼠GLP-2(1-33) | Ala2->Gly2 | 196% | 0% |
[Tyr1]大鼠GLP-2(1-33) | His1->Tyr1 | 81% | 100% |
[Ala4]大鼠GLP-2(1-33) | Gly4->Al4a | 59% | 72% |
[Glu3]大鼠GLP-2(1-33) | Asp3->Glu3 | 65% | 50% |
[Leu10]大鼠GLP-2(1-33) | Met10->Leu10 | 51% | |
[Nle10]大鼠GLP-2(1-33) | Met10->Nle10 | 100% | |
[Lys20]大鼠GLP-2(1-33) | Arg20->Lys20 | 120% | |
[Ser2,Gln3]hGLP-2(1-33) | Ala2->Ser2,Asp3->Glu3 | 11% | 0% |
[Val23,Gln24]hGLP-2(1-33) | Ile23->Val23,Asn24->Gln24 | 82% | |
[Val2]GLP-2(1-33) | Ala2->Val2,TPA | 145% | 0% |
Degu GLP-2 | 天然drgu序列 | 70% | |
[Tyr9,Ser10,Lys11,Tyr12,des-Ile13] | Glu9->Tyr9,Met10->Ser10,Asn11 | 94% | |
hGLP-2(1-33) | ->Lys11,Thr12->Tyr12,并且缺失Ile13 | ||
[Gly2,Ala8]hGLP-2(1-33) | Ala2->Gly2,Asp8->Ala8 | 120% | |
[Gly2,Ala11]hGLP-2(1-33) | Ala2->Gly2,Asn11->Ala11 | 150% | |
[Gly2,Ala21]hGLP-2(1-33) | Ala2->Gly2,Asp21->Ala21 | 125% | |
[Gly2,Ala24]hGLP-2(1-33) | Ala2->Gly2,Asn24->Ala24 | 139% | 0% |
[Gly2,Ala25]hGLP-2(1-33) | Ala2->Gly2,Trp25->Ala25 | 18% | |
[Gly2,Ala26]hGLP-2(1-33) | Ala2->Gly2,Leu26->Ala26 | 28% | |
[Gly2,Ala27]hGLP-2(1-33) | Ala2>Gly2,Ile27->Ala27 | 82% | |
[Gly2,Ala9]hGLP-2(1-33) | Ala2->Gly2,Glu9->Ala9 | 112% | |
[Gly2,Ala10]hGLP-2(1-33) | Ala2->Gly2,Met10->Ala10 | 82% | |
[Gly2,Ala12]hGLP-2(1-33) | Ala2->Gly2,Thr12->Ala12 | 67% | |
[Gly2,Ala13]hGLP-2(1-33) | Ala2->Gly2,Ile13->Ala13 | 67% | |
[Gly2,Ala14]hGLP-2(1-33) | Ala2->Gly2,Leu14->Ala14 | 30% | |
[Gly2,Ala16]hGLP-2(1-33) | Ala2->Gly2,Asn16>Ala16 | 130% | |
[Gly2,Ala17]hGLP-2(1-33) | Ala2->Gly2,Leu17->Ala17 | 130% | |
[Gly2,Ala20]hGLP-2(1-33) | Ala2->Gly2,Arg20->Ala20 | 105% | |
[Gly2,Ala23]hGLP-2(1-33) | Ala2->Gly2,Ile23->Ala23 | 24% | |
[Gly2,Ala28]hGLP-2(1-33) | Ala2->Gly2,Gln28->Ala28 | 130% | |
[Gly2,Ala30]hGLP-2(1-33) | Ala2->Gly2,Lys30->Ala30 | 24% | |
[Gly2,Ala31]hGLP-2(1-33) | Ala2->Gly2,Ile31->Ala31 | 100% | |
[Gly2]hGLP-2(1-33) | Ala2->Gly2, | 300% | 0% |
[Ala1,Gly2]hGLP-2(1-33) | His1->Ala1,Ala2->Gly2, | 53% | 0% |
[Gly2,Ala3]hGLP-2(1-33) | Ala2->Gly2,Asp3->Ala3 | 44% | 0% |
[Gly2,Ala4]hGLP-2(1-33) | Ala2->Gly2,Gly4->Ala4 | 100% | 0% |
[Gly2,Ala5]hGLP-2(1-33) | Ala2->Gly2,Ser5->Ala5 | 136% | 0% |
[Gly2,Ala6]hGLP-2(1-33) | Ala2->Gly2,Phe6->Ala6 | 67% | |
[Gly2,Ala7]hGLP-2(1-33) | Ala2->Gly2,Ser7->Ala7 | 82% | |
[Pro1]hGLP-2(1-33) | His1->Pro1 | 12% | 0% |
[Met(O)10]大鼠GLP-2(1-33) | Met10亚砜 | 18% | |
[Gln20]hGLP-2(1-33) | Arg20->Gln20 | 80% | |
[Asp1]hGLP-2(1-33) | His1->Asp1 | 60% | 0% |
[tBuGly2]hGLP-2 | Ala2->t-buty1-Gly2 | 123% | 0% |
[Tyr34]hGLP-2(1-34) | 加入C端Tyr | 135% | |
[Asp2]hGLP-2(1-33) | Ala2->Asp2 | 83% | 0% |
[Glu2]hGLP-2(1-33) | Ala2->Glu2 | 93% | 0% |
[Phe2]hGLP-2(1-33) | Ala2->Phe2 | 50% | 0% |
[His2]hGLP-2(1-33) | Ala2->His2 | 0% | 0% |
[Ile2]hGLP-2(1-33) | Ala2->Ile2 | 90% | 0% |
[Lys2]hGLP-2(1-33) | Ala2->Lys2 | 90% | 0% |
[Met2]hGLP-2(1-33) | Ala2->Met2 | 170% | 0% |
[Asn2]hGLP-2(1-33) | Ala2->Asn2 | 67% | 0% |
[Pro2]hGLP-2(1-33) | Ala2->Pro2 | 50% | 16% |
[Gln2]hGLP-2(1-33) | Ala2->Gln2 | 100% | 0% |
[Ser2]hGLP-2(1-33) | Ala2->Ser2 | 167% | 0% |
[Thr2]hGLP-2(1-33) | Ala2->Thr2 | 117% | 0% |
[Val2]hGLP-2(1-33) | Ala2->Val2 | 180% | 13% |
[Tyr2]hGLP-2(1-33) | Ala2->Tyr2 | 57% | 0% |
[D-Ala2hGLP-2(1-33) | Ala2->D-Ala2 | 130% | 0% |
hGLP-2(1-33) | 天然人类序列 | 100% | 60% |
[desNH2Tyr1]hGLP-2(1-33) | His1->脱氨-Tyr1 | 125% | 15% |
[Thr5]hGLP-2(1-33) | Ser5->Thr5 | 73% | |
[Ser16,Arg17,Arg18]hGLP-2(1-33) | Asn16->Ser16,Leu17->Arg17,Ala18->Arg18 | 59% | |
[Asn33]hGLP-2(1-33) | Asp33->Asn33 | 91% | |
[Pen2]hGLP-2(1-33) | Ala2->L-青霉胺2 | 58% | 20% |
[bAla2]hGLP-2(1-33) | Ala2->β-Ala2 | 118% | 0% |
[aAbu2]hGLP-2(1-33) | Ala2->α-氨基丁酸2 | 84% | 49% |
[Nval2]hGLP-2(1-33) | Ala2->Nval2(正缬氨酸) | 111% | 0% |
[PhGly2]hGLP-2(1-33) | Ala2->L-苯基-Gly2 | 37% | 0% |
[Agm34]hGLP-2(1-33) | 加入C端鲱精胺(Agm为脱羧Arg) | 97% | |
[Arg30]hGLP-2(1-33) | Lys30->Arg30 | 103% | 59% |
[Pro3]hGLP-2(1-33) | Asp3->Pro3 | 140% | 0% |
[Ala5,Ala7]hGLP-2(1-33) | Ser5->Ala5,Ser7->Ala7 | 108% | 77% |
[Tyr1,Gly2]hGLP-2(1-33) | His1->Tyr1,Ala2->Gly2 | 241% | 0% |
[Glu33]hGLP-2(1-33) | Asp33->Glu33 | 121% | 55% |
[Phe25]hGLP-2(1-33) | Trp25->Phe25 | 114% | 54% |
[Tyr25]hGLP-2(1-33) | Trp25->Tyr25 | 64% | 48% |
[Gly2,Tyr34]hGLP-2(1-34) | Ala2->Gly2+C端Tyr | 297% | 0% |
[Aib2]hGLP-2(1-33) | Ala2->氨基异丁酸2 | 202% | 0% |
[Gly2,Arg34]hGLP-2(1-34) | Ala2->Gly2+C端Arg | ~250% | 0% |
Claims (91)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US63127396A | 1996-04-12 | 1996-04-12 | |
US08/631,273 | 1996-04-12 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1244872A CN1244872A (zh) | 2000-02-16 |
CN1268640C true CN1268640C (zh) | 2006-08-09 |
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Application Number | Title | Priority Date | Filing Date |
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CNB971953317A Expired - Lifetime CN1268640C (zh) | 1996-04-12 | 1997-04-11 | 胰高血糖素样肽-2的类似物 |
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Country | Link |
---|---|
EP (5) | EP2218734B1 (zh) |
JP (3) | JP4148994B2 (zh) |
CN (1) | CN1268640C (zh) |
AT (2) | ATE227309T1 (zh) |
AU (1) | AU733857B2 (zh) |
BR (1) | BRPI9708566B8 (zh) |
CA (1) | CA2251576C (zh) |
DE (2) | DE60142885D1 (zh) |
DK (2) | DK1231219T3 (zh) |
ES (2) | ES2351661T3 (zh) |
FR (1) | FR13C0013I2 (zh) |
HK (3) | HK1033324A1 (zh) |
LU (1) | LU92153I2 (zh) |
NZ (1) | NZ332281A (zh) |
PT (2) | PT906338E (zh) |
WO (1) | WO1997039031A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102942626A (zh) * | 2009-03-05 | 2013-02-27 | 连云港恒邦医药科技有限公司 | 胰高血糖素样肽-2 类似物及其制备方法和用途 |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6184201B1 (en) | 1995-04-14 | 2001-02-06 | Nps Allelix Corp. | Intestinotrophic glucagon-like peptide-2 analogs |
US5990077A (en) * | 1995-04-14 | 1999-11-23 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
US5834428A (en) | 1995-04-14 | 1998-11-10 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
US6852690B1 (en) | 1995-08-22 | 2005-02-08 | Amylin Pharmaceuticals, Inc. | Method and composition for enhanced parenteral nutrition |
EP2218734B1 (en) * | 1996-04-12 | 2013-06-05 | 1149336 Ontario Inc. | Glucagon-like peptide-2 analogs |
US5952301A (en) * | 1996-12-10 | 1999-09-14 | 1149336 Ontario Inc. | Compositions and methods for enhancing intestinal function |
CA2236519C (en) | 1997-05-02 | 2011-09-13 | 1149336 Ontario Inc. | Methods of enhancing functioning of the large intestine |
AU746633B2 (en) * | 1997-05-16 | 2002-05-02 | 1149336 Ontario Inc. | Methods of enhancing functioning of the upper gastrointestinal tract |
JP2002504527A (ja) * | 1998-02-27 | 2002-02-12 | ノボ ノルディスク アクティーゼルスカブ | 部分的に組織化したミセル様凝集物を形成する25%を越えるヘリックス成分を有するglp−2誘導体 |
WO1999058144A1 (en) * | 1998-05-11 | 1999-11-18 | 1149336 Ontario Inc. | Methods of enhancing functioning of the large intestine |
GB9930882D0 (en) | 1999-12-30 | 2000-02-23 | Nps Allelix Corp | GLP-2 formulations |
US7371721B2 (en) | 2000-09-18 | 2008-05-13 | Sanos Bioscience A/S | Use of GLP-2 and related compounds for the treatment, prevention, diagnosis, and prognosis of bone-related disorders and calcium homeostasis related syndromes |
DE60134251D1 (de) | 2000-09-18 | 2008-07-10 | Sanos Bioscience As | Verwendung von glp-2-peptiden |
WO2004035624A2 (en) * | 2002-10-14 | 2004-04-29 | Novo Nordisk A/S | Glucagon - like peptide - 2 variants |
ATE502665T1 (de) | 2003-02-04 | 2011-04-15 | Novo Nordisk As | Injektionsvorrichtung mit drehbarer dosiseinstellungsvorrichtung |
WO2005019262A1 (en) * | 2003-08-21 | 2005-03-03 | Novo Nordisk A/S | Purification of glucagon-like peptides |
ES2642214T3 (es) | 2004-01-21 | 2017-11-15 | Novo Nordisk Health Care Ag | Conjugación de péptidos mediante transglutaminasa |
DK1809318T3 (da) | 2004-11-01 | 2013-09-08 | Nps Pharma Inc | Behandling af korttarmssyndrom-patienter med tyktarmskontinuitet |
ATE498631T1 (de) * | 2005-05-04 | 2011-03-15 | Zealand Pharma As | Glucagon-like-peptide-2- (glp-2-) analoga |
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Cited By (2)
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CN102942626A (zh) * | 2009-03-05 | 2013-02-27 | 连云港恒邦医药科技有限公司 | 胰高血糖素样肽-2 类似物及其制备方法和用途 |
CN102942626B (zh) * | 2009-03-05 | 2015-11-04 | 江苏豪森医药集团有限公司 | 胰高血糖素样肽-2类似物及其制备方法和用途 |
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