GLUCAGON-LIKE PEPTIDE-1 ANALOGSDisclosed are glucagon-like peptide-1 (GLP-1) compounds with modifications at one or more of the following positions: 7, 8, 12, 16, 18, 19, 20, 22, 25, 27, 30, 33, and 37. Methods of treating a subject in need of GLP-1 receptor stimulation using these GLP-1 compounds are also disclosed.A GLP-1 compound comprising the amino acid sequence of formula 1 (SEQ ID NO:l)Xaa -Xaa8-Glu-Gly-Thr-Xaaι2-Thr-Ser-Asp-Xaai6-Ser- Xaa18-Xaai9-Xaa20-Glu-Xaa22-Gln-Ala-Xaa25-Lys-Xaa27- Phe-Ile-Xaa3cι-Trp-Leu-Xaa33-Lys-Gly-Arg-Xaa37 Formula 1 (SEQ ID NO: 1)wherein:Xaa7 is: L-histidine, D-histidine, desamino-histidine, 2- amino-histidine, β-hydroxy-histidine, homohistidine, α-fluoromethyl-histidine, or α- methyl-histidine ;Xaa8 is: Ala, Gly, Val, Leu, He, Ser, or Thr;Xaai2 is: Phe, Trp, or Tyr;Xaai6 is: Val, Trp, He, Leu, Phe, or Tyr; Xaaie is: Ser, Trp, Tyr, Phe, Lys, He, Leu, or Val ;Xaai9 is: Tyr, Trp, or Phe;Xaa2o is: Leu, Phe, Tyr, or Trp;Xaa22 is: Gly, Glu, Asp, Lys ;Xaa25 is: Ala, Val, He, or Leu; Xaa27 is: Glu, He, or Ala;Xaa30 is: Ala or GluXaa33 is: Val, or He; andXaa37 is: Gly, His, NH2, or is absent.provided that the GLP-1 compound does not have the sequence of GLP-1 (7-37) OH, GLP-1 (7-36) -NH2, Gly8-GLP- l(7-37)OH, Gly8-GLP-1(7-36)NH2, Val8-GLP-1 (7-37) OH, Val8-GLP-1 (7-36)NH2, Lue8-GLP-1 (7-37) OH, Leu8-GLP-1 (7- 36)NH2, He8-GLP-1 (7-37)OH, He8-GLP-1 (7-36) NH2, Ser8- GLP-1 (7-37)OH, Ser8-GLP-1 (7-36) NH2, Thr8-GLP-1 (7-37) OH, Thr8-GLP-1(7-36)NH2, Val8 -Tyr12 -GLP-1 (7-37) OH, Val8-Tyr -12 - GLP-1 ( 7 - 36 ) NH2 Val8 -Tyr16 -GLP-1 (7-37) OH, Val8- Tyr16- GLP-1 (7-36)NH2 Val8-Glu22-GLP-l(7-37)OH, Val8- Glu22- GLP-1 (7-36)NH2 Gly8-Glu22-GLP-l(7-37)OH, Gly8- Glu22- GLP-1 (7-36)NH2 Val8-Asp22-GLP-l(7-37)OH, Val8-Asp -2'2 GLP-1 (7-36)NH2 Gly8-Asp22-GLP-1 (7-37) OH, Gly8-Asp 22 GLP-1 (7-36)NH2 Val8-Lys22-GLP-l(7-37)OH, Val8-Lys 22 GLP-1 (7-36)NH2 Gly8-Lys22-GLP-l(7-37)OH, Gly8-Lys 22 GLP-1 (7-36)NH2 Leu8-Glu22-GLP-1 (7-37) OH, Leu8-Glu 22 GLP-1 (7-36)NH2 Ile8-Glu22-GLP-1 (7-37) OH, Ile8-Glu22- GLP-1 (7-36)NH2 Leu8 -Asp22 -GLP-1 (7-37) OH, Leu8-Asp 22 GLP-1 (7-36)NH2 He8-Asp22-GLP-l(7-37)OH, Ile8- Asp 22 GLP-1 (7-36)NH2 Leu8-Lys22-GLP-1 (7-37) OH, Leu8-Lys22- GLP-1 (7-36)NH2 Ile8-Lys22-GLP-1 (7-37) OH, Ile8- Lys22- GLP-1 (7-36)NH2 Ser8-Glu22-GLP-1 (7-37) OH, Ser8- Glu22- GLP-1 (7-36)NH2 Thr8-Glu22-GLP-l(7-37)OH, Thr8- Glu22- GLP-1 (7-36)NH2 Ser8-Asp22-GLP-1 (7-37) OH, Ser8-Asp -22 GLP-1 (7-36)NH2 Thr8 -Asp22 -GLP-1 (7-37) OH, Thr8- Asp 22 GLP-1 (7-36)NH2 Ser8-Lys22-GLP-l(7-37)OH, Ser8- Lys 22 GLP-1 (7-36)NH2 Thr8 -Lys22 -GLP-1 (7-37) OH, Thr8- Lys 22 GLP-1 (7-36)NH2 Glu22-GLP-l(7-37)OH, Glu22-GLP-1 (7- 36)NH2, Asp22-GLP-1 (7-37) OH, Asp22-GLP-1 (7-36) NH2, Lys22- GLP-l(7-37)OH, Lys2 -GLP-1 (7-36) NH2, Val8-Ala27-GLP-1 (7- 37) OH, Val8-Glu2 -Ala27-GLP-1 (7-37) OH, Val8-Glu30-GLP- 1(7-37) OH, Val8-Glu30-GLP-1 (7-36) NH2, Gly8-Glu30-GLP-1 (7- 37) OH, Gly8-Glu30-GLP-1(7-36)NH2, Leu8-Glu30-GLP-1 (7- 37) OH, Leu8-Glu30-GLP-1(7-36)NH2, He8-Glu30-GLP-1 (7- 37) OH, He8-Glu30-GLP-1(7-36)NH2, Ser8-Glu30-GLP-1 (7- 37) OH, Ser8-Glu30-GLP-1(7-36)NH2, Thr8-Glu30-GLP-1 (7- 37) OH, Thr8-Glu30-GLP-1(7-36)NH2, Val8-His37-GLP-1 (7- 37) OH, Val8-His37-GLP-1(7-36)NH2, Gly8-His37-GLP-1 (7- 37) OH, Gly8-His37-GLP-1(7-36)NH2, Leu8-His37-GLP-1 (7- 37) OH, Leu8-His37-GLP-1(7-36)NH2, He8-His37-GLP-1 (7- 37) OH, He8-His37-GLP-1(7-36)NH2, Ser8-His37-GLP-1 (7- 37) OH, Ser8-His37-GLP-1 (7-36) NH2, Thr8-His37-GLP-1 (7- 37) OH, Thr8-His37-GLP-1 (7-36) NH2.
글루카곤-유사 펩티드-1 유사체위치 7, 8, 12, 16, 18, 19, 20, 22, 25, 27, 30, 33 및 37 중 하나 이상에서 변형이 일어난 글루카곤 유사 펩티드-1 (GLP-1) 화합물을 개시한다. 이들 GLP-1 화합물을 사용하여 GLP-1 수용체 자극이 필요한 대상체를 치료하는 방법도 개시한다.하기 화학식 I (서열 1)의 아미노산 서열을 포함하는 GLP-1 화합물: <화학식 I (서열 1)>  상기 식에서, Xaa7은 L-히스티딘, D-히스티딘, 데스아미노-히스티딘, 2-아미노-히스티딘, β-히드록시-히스티딘, 호모히스티딘, α-플루오로메틸-히스티딘 또는 α-메틸-히스티딘이고; Xaa8은 Ala, Gly, Val, Leu, Ile, Ser 또는 Thr이고; Xaa12는 Phe, Trp 또는 Tyr이고; Xaa16은 Val, Trp, Ile, Leu, Phe 또는 Tyr이고; Xaa18은 Ser, Trp, Tyr, Phe, Lys, Ile, Leu 또는 Val이고; Xaa19는 Tyr, Trp 또는 Phe이고; Xaa20은 Leu, Phe, Tyr 또는 Trp이고; Xaa22는 Gly, Glu, Asp 또는 Lys이고; Xaa25는 Ala, Val, Ile 또는 Leu이고; Xaa27은 Glu, Ile 또는 Ala이고; Xaa30은 Ala 또는 Glu이고; Xaa33은 Val 또는 Ile이며; Xaa37은 Gly, His, NH2이거나 또는 결실되나, 단, GLP-1 화합물은 하기 서열은 갖지 않는다:  