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.

Teprotide
Names
IUPAC name
5-oxo-L-prolyl-L-tryptophyl-L-prolyl-N5-(diaminomethylidene)-L-ornithyl-L-prolyl-L-glutaminyl-L-isoleucyl-L-prolyl-L-proline
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
UNII
  • InChI=1S/C53H76N14O12/c1-3-29(2)43(51(77)66-25-9-16-39(66)50(76)67-26-10-17-40(67)52(78)79)63-45(71)34(18-20-41(54)68)60-46(72)37-14-7-23-64(37)48(74)35(13-6-22-57-53(55)56)61-47(73)38-15-8-24-65(38)49(75)36(62-44(70)33-19-21-42(69)59-33)27-30-28-58-32-12-5-4-11-31(30)32/h4-5,11-12,28-29,33-40,43,58H,3,6-10,13-27H2,1-2H3,(H2,54,68)(H,59,69)(H,60,72)(H,61,73)(H,62,70)(H,63,71)(H,78,79)(H4,55,56,57)/t29-,33-,34-,35-,36-,37-,38-,39-,40-,43-/m0/s1 checkY
    Key: UUUHXMGGBIUAPW-CSCXCSGISA-N checkY
  • InChI=1S/C53H76N14O12/c1-3-29(2)43(51(77)66-25-9-16-39(66)50(76)67-26-10-17-40(67)52(78)79)63-45(71)34(18-20-41(54)68)60-46(72)37-14-7-23-64(37)48(74)35(13-6-22-57-53(55)56)61-47(73)38-15-8-24-65(38)49(75)36(62-44(70)33-19-21-42(69)59-33)27-30-28-58-32-12-5-4-11-31(30)32/h4-5,11-12,28-29,33-40,43,58H,3,6-10,13-27H2,1-2H3,(H2,54,68)(H,59,69)(H,60,72)(H,61,73)(H,62,70)(H,63,71)(H,78,79)(H4,55,56,57)/t29-,33-,34-,35-,36-,37-,38-,39-,40-,43-/m0/s1
  • O=C(O)[C@H]7N(C(=O)[C@H]6N(C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]5N(C(=O)[C@@H](NC(=O)[C@H]4N(C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)Cc3c2ccccc2[nH]c3)CCC4)CCC/N=C(\N)N)CCC5)CCC(=O)N)[C@@H](C)CC)CCC6)CCC7
Properties
C53H76N14O12
Molar mass 1101.257
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Isolation and synthesis

The antihypertensive effects of teprotide were first observed by Sergio Ferreira in 1965 [1] and it was first isolated by Ferreira et al.[2] along with eight other peptides in 1970. Teprotide was synthesized in 1970 by Ondetti et al.[3] 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.[4] 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.[5] Many ACE inhibitors have been developed since this time but this was the start of them.

References
  1. Ferreira, Sergio (February 1965). "A bradykinin-potentiating factor (bpf) present in the venom of bothrops jararaca". British Journal of Pharmacology. 24: 169–169. doi:10.1111/j.1476-5381.1965.tb02091.x. PMC 1704050. PMID 14302350.
  2. Ferreira, Sergio H.; Diana C. Bartelt; Lewis J. Greene (June 1970). "Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom". Biochemistry. 9 (13): 2583–2593. doi:10.1021/bi00815a005. PMID 4317874.
  3. Ondetti, Miguel A.; Nina J. Williams; Emily F. Sabo; Josip Pluscec; Eugene R. Weaver; Octavian Kocy (October 1971). "Angiotensin-converting enzyme inhibitors from the venom of bothrops jararaca. Isolation, elucidation of structure, and synthesis". Biochemistry. 10 (22): 4033–4039. doi:10.1021/bi00798a004. PMID 4334402.
  4. Bianchi, A.; D.B. Evans; M. Cobb; M.T. Peschka; T.R. Schaeffer; R.J. Laffan (July 1973). "Inhibition by SQ 20881 of vasopressor response to angiotensin I in conscious animals". European Journal of Pharmacology. 23 (2): 90–96. doi:10.1016/0014-2999(73)90248-3. PMID 4354808.
  5. Cushman, D.W.; M.A. Ondetti (April 1991). "History of the design of captopril and related inhibitors of angiotensin converting enzyme". Hypertension. 17 (4): 589–592. doi:10.1161/01.hyp.17.4.589. PMID 2013486.
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