Introduce GLP-1 Analogues
There are several GLP-1 Analogues drugs developed by first-class pharmaceutical companies and widely used to cure type 2 diabetes. One is a long-acting drug developed by Novo Nordisk based on the structure of Lilalutide. The latest generation of GLP-1 analog has a better therapeutic effect on type 2 diabetes.
Another is developed by Eli Lilly, a double agonist of the GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 receptor. Both GIP and GLP-1 are hormones secreted by the intestine, which can promote insulin secretion. It integrates two insulin-promoting effects into a single molecule, representing a new class of drugs for treating type 2 diabetes.
The Side Chain Enhanced By AEEA-AEEA
Both GLP-1 Analogues‘ side chains are modified by a short chain of PEG(AEEA-AEEA), hence both hydrophilicity is enhanced dramatically. After using an AEEA-OH spacer(AEEA-AEEA) to modify the side chain, it can not only closely bind with albumin, and cover up the hydrolysis site of DPP-4 enzyme, but also reduce renal excretion, prolong the biological half-life, and achieve the effect of long circulation.
The Similar Strutures
From the above pictures, both GLP-1 Analogues have very similar molecular structures. The only difference is the number of Carbon atoms in fatty acid on the side chain.
Blocks on the Side Chain
Comparing the side chains as bellows:
There are the same single blocks in both side chains: AEEA、Glu、C18 or C20 fatty acid.
We launch a series of products according to the structure and different blocks.
Products Series
1. Single Block
| AEEA | Fmoc-AEEA | AEEA-OH·Hcl | Boc-AEEA-OH | AEEA |
| Glu | Fmoc-Glu-OtBu | Glu-OtBu | ||
| Lys | Fmoc-Lys-OH Hcl | Fmoc-Lys(Boc)-OH | ||
| Di-fatty acid | Octadecanedioic acid mono(1,1-dimethylethyl) ester | 20-(tert-Butoxy)-20-oxoicosanoic acid |
2. Two Blocks
| Lys+AEEA | ||
| AEEA+AEEA | Fmoc-AEEA-AEEA-OH | AEEA-AEEA |
| AEEA+Glu | ||
| Glu+Di-fatty acid | tBuO-Ste-Glu(OtBu)-OH | C20-OtBu-Glu-OtBu |
3. Three and Four Blocks
| Lys+AEEA+AEEA | |
| AEEA+AEEA+Glu | |
| Lys+AEEA+AEEA+Glu |
4. Total Side Chain
| HO-Ste-Glu(AEEA-AEEA-OSu)-OH |
| tBuO-Ste-Glu(AEEA-AEEA-OH)OtBu |
| tBuO-Ste-Glu(AEEA-AEEA-OSu)-OtBu |
| tBuO-Ste-Glu(AEEA-AEEA-ONa)-OtBu |
| Fmoc-L-Lys[Oct-(otBu)-Glu-(otBu)-AEEA-AEEA]-OH |
| Fmoc-L-Lys[Oct-(otBu)-Glu-(otBu)-AEEA-AEEA]-OH |
| Fmoc-L-Lys[C20-OtBu-Glu(OtBu)-AEEA-AEEA]-OH |
