Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom

Ferreira, Sergio H.; Bartelt, Diana C.; Greene, Lewis J.

doi:10.1021/bi00815a005

Cited by 547 publications

(282 citation statements)

References 34 publications

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“…Ferreira and his co-workers subsequently isolated a number of peptides from the venom and determined their amino acid composition. For one of the peptides, BPP 5a , also the sequence of amino acids was elucidated (Ferreira, Bartelt & Greene 1970).…”

Section: Academic Lines Of Research and Their Industrial Continuationmentioning

confidence: 99%

Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Adam

2005

Studies in History and Philosophy of Science Part C: Studies in

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Appears in Studies in History and Philosophy of Biological and Biomedical Sciences 36 (2005). AbstractRational drug design is a method for developing new pharmaceuticals that typically involves the elucidation of fundamental physiological mechanisms. It thus combines the quest for a scientific understanding of natural phenomena with the design of useful technology and hence integrates epistemic and practical aims of research and development. Case studies of the rational design of the cardiovascular drugs propranolol, captopril and losartan provide insights into characteristics and conditions of this integration. Rational drug design became possible in the 1950s when theoretical knowledge of drug-target interaction and experimental drug testing could interlock in cycles of mutual advancement. The integration does not, however, diminish the importance of basic research for pharmaceutical development. Rather, it can be shown that still in the 1990s, linear processes of innovation and the close combination of practical and epistemic work were interdependent.

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Section: Academic Lines Of Research and Their Industrial Continuationmentioning

confidence: 99%

Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Adam

2005

Studies in History and Philosophy of Science Part C: Studies in

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“…The synthetic and natural deca-peptide, however, differ in potency: thus PlO has an ID50 of 3f4 ,ug/ml, almost 4 times that obtained for IV-1-A, 09 ,ug/ml. The explanation for this discrepancy may lie in the fact that the natural peptides tested were those prepared by Ferreira et al (1970a) whereas the synthetic peptides used here were synthesized by Ondetti et al (1970). The structure of PlO was elucidated by Ondetti et al, and although it has the same amino-acid composition as the natural peptide IV-1-A, there may be differences in sequence between the two peptides.…”

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confidence: 99%

“…BPF also inhibits the peptidases catalysing the formation of angiotensin II from angiotensin I-' converting enzyme' (Bakhle, 1968;Bakhle, Reynard & Vane, 1969). BPF has been separated into its component peptides (Ferreira, Bartelt & Greene, 1970a) and several of these are potent inhibitors of converting enzyme (Ferreira, Greene, Alabaster, Bakhle & Vane, 1970b). Recently, the structure of some of these peptides has been established and their synthesis accomplished (Greene, Stewart & Ferreira, 1970;Ondetti, Williams, Sabo, Plusec, Weaver & Kocy, 1970).…”

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Inhibition of angiotensin I converting enzyme by venom peptides

Bakhle

1971

British J Pharmacology

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“…The enzyme is a glycoprotein (5,6) that is localized on the luminal surface of vascular endothelial cells in anatomic juxtaposition to the circulation (7)(8)(9). Specific chemical inhibitors of its activity (10)(11)(12) can reverse experimental renovascular hypertension (13)(14)(15)(16)(17) and can reduce blood pressure in a substantial fraction of human hypertensive disease (18,19). These considerations suggest that converting enzyme provides an unusual opportunity for exploring the possibility that the activity of an enzyme can be inhibited by specific anticatalytic antibody in vivo and that a pathologic process can thus be immunologically controlled.…”

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Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme.

Markle¹,

Sonnenblick

Conroy

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

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Goat antibodies developed against pure rabbit pulmonary an iotensin-converting enzyme (pe tidyl dipeptidase, EC 3.4.1) were administered intravenousyto rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states. Angiotensin-converting enzyme (EC 3.4.15.1) is a COOHterminal peptidyl dipeptidase that catalyzes release of His-Leu from angiotensin I (1) to yield angiotensin II, the biologically active vasopressor octapeptide of the renin-angiotensin system (2, 3). It also liberates Phe-Arg and Ser-Pro from bradykinin (4, 5), thereby inactivating this vasodepressor nonapeptide. The enzyme is a glycoprotein (5, 6) that is localized on the luminal surface of vascular endothelial cells in anatomic juxtaposition to the circulation (7)(8)(9). Specific chemical inhibitors of its activity (10-12) can reverse experimental renovascular hypertension (13-17) and can reduce blood pressure in a substantial fraction of human hypertensive disease (18, 19). These considerations suggest that converting enzyme provides an unusual opportunity for exploring the possibility that the activity of an enzyme can be inhibited by specific anticatalytic antibody in vivo and that a pathologic process can thus be immunologically controlled.To investigate this possibility we isolated pure rabbit pulmonary converting enzyme (5, 6) and then developed goat antibodies against it (20). When these antibodies were administered intravenously to rabbits, even in relatively small amounts, they caused an immune-dependent lethal reaction that could not be explained solely on the basis of their anticatalytic effect (21 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisenmnt" in accordance with 18 U. S. C. §1734 solely to indicate this fact.In order to circumvent this lethal reaction we examined immunologic homology of the rabbit enzyme with enzymes from other species by using the antibodies to rabbit enzyme as a probe (24). We found that these antibodies inhibited rat converting activity in vitro and were well tolerated by this heterologous recipient animal even at very high dosage. It has not yet been established whether the lethal effect in rabbits as contrasted with rats is a universal complication of administration of antibody to converting enzyme to homologous recipient animals or a species-specific phenomenon associated with the rabbit. The recent isolation of pure canine converting enzyme and goat antibodies directed against it (25) provides another experimental system ...

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Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom

Cited by 547 publications

References 34 publications

Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Inhibition of angiotensin I converting enzyme by venom peptides

Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme.

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