Succinyl L-proline

Teprotide was used as an active antihypertensive drug in patients with essential hypertension, but due to a lack of oral activity it was administered parenterally. Teprotide has been the first lead for novel orally active AC E-inhibitors, with three important lead-molecules having been discovered as follows succinyl-L-proline, (2S)-methylsuccinyl-L-proline and 3-mercaptopropanoyl-L-proline affording at the end the first successful drug in this class captopril, as discovered by Ondetti, Rubin and Cushman [1] (Fig. 6.3). 

Atherosclerosis NMR GC-MS Glutamate Ketoglutarate Succinyl-CoA 4-OH-L-proline Creatine Pyruvate Mai ate Glycolate (20)... 

Importance of the R substituent. Studies using succinyl derivatives possessing different C-terminal amino acids. It was shown that sucpinyl-L-proline was the most potent inhibitor [83]. Other studies have indicated that C-terminal aromatic amino acid and leucine residues are also acceptable, but are less efficient than the proline residue for ACE inhibition [79], It has been suggested that the superiority of L-proline is due to its rigid structure which may lock the carboxyl group into a favourable conformation for interaction with the positively charged residue at the active site of the enzyme. 

To find the most efficient selectors in the library, blue and red dye-labeled enantiomeric probe molecules 6 and 7 were prepared by linking pentafluorophenyl esters of L- and D-proline with Disperse Blue 3 and Disperse Red 1, respectively, through an isophthaloyl (shown in structures 6 and 7) or a succinyl moiety. Eor detection, a... 

---