Teprotide is nonapeptide which has been isolated from the snake Bothrops jararaca

Bothrops jararaca

Bothrops jararaca is a venomous pit viper species found in southern Brazil, Paraguay and northern Argentina. The species name is derived from the Tupi words yarará and ca, which means "large snake." Within its range it is often abundant and is an important cause of snakebite...

. It is an angiotensin converting enzyme inhibitor (ACE inhibitor

ACE inhibitor

ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...

), which inhibits the conversion of angiotensin I to angiotensin II and may potentiate some of the pharmacological actions of bradykinin

Bradykinin

Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...

. It has a molecular formula of C₅₃H₇₆N₁₄O₁₂ and has been looked at 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.