Teprotide

Teprotide is nonapeptide which has been isolated from the snake Bothrops jararaca. It is an angiotensin converting enzyme inhibitor (ACE inhibitor) which inhibits the conversion of angiotensin I to angiotensin II and may potentiate some of the pharmacological actions of bradykinin. It has a molecular formula of C53H76N14O12 and has been investigated as an antihypertension agent.

Isolation and synthesis
The antihypertensive effects of teprotide were first observed by Sergio Ferreira in 1965  and it was first isolated by Ferreira et al. along with eight other peptides in 1970. Teprotide was synthesized in 1970 by Ondetti et al. and from there its antihypertensive properties were studied more closely.

Medical use
Teprotide was chosen as a lead because of its long-lasting in vivo activity. This was demonstrated by Bianchi et al. by administering teprotide to dogs and rats and observing that it inhibited the vasopressor response induced by angiotensin I. Teprotide was shown to be an effective antihyperension agent but it had limited use because of its expense and lack of oral activity. It was found that teprotide inhibits the enzyme that converts angiotensin I to angiotensin II. From this researchers conducted structure-activity studies which allowed them to identify the active binding site of the ACE which allowed for the development of antihypertension drugs to be developed. Captopril was the first antihypertension drug developed by Ondetti and Cushman. Many ACE inhibitors have been developed since this time but this was the start of them.