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PFIZER-BRITISH SCIENTIFIC COLLABORATION PUBLISHES KEY HYPERTENSION FINDINGS

 PFIZER-BRITISH SCIENTIFIC COLLABORATION
 PUBLISHES KEY HYPERTENSION FINDINGS
 GROTON, Conn., June 23 /PRNewswire/ -- Scientists from research collaboration between Pfizer Central Research in Groton and Birkbeck College, University of London, England, has published the first detailed scientific explanation of the specificity of human renin, a key enzyme in the control of blood pressure, Pfizer Central Research announced today.
 The findings were reported in the June 11, 1992, issue of Nature, the prestigious scientific journal published by Macmillan Magazines Ltd. of London. The authors included six Pfizer scientists and 12 scientists from Birkbeck.
 Renin is normally produced in small amounts by the kidney and released into the bloodstream, where its only known role is in the regulation of blood pressure. This specificity makes renin an attractive target for the development of new anti-hypertension medicines.
 The enzyme renin splits another blood protein called agiotensinogen, releasing a small fragment called angiotensin I. Further biological processing of angiotensin I produces angiotensin II, which directly elevates blood pressure. The overall process is called the "renin- angiotensin cascade." Scientists have been searching for a drug to block renin for more than 20 years.
 Many scientists believe that the renin-angiotensin cascade can be controlled by developing drugs to block the binding site on the renin molecule. If so, it would be possible to develop anti-hypertension drugs with few, or no, side effects. Levels of angiotensin II found in hypertension patients have also been linked to congestive heart failure, cardiovascular and peripheral hypertrophy and renal disease.
 Understanding the interaction of the renin enzyme with compounds is critical to the process of developing renin-blocking drugs because the binding site changes shape when a molecule interacts with it. The Pfizer/Birkbeck team was able to show the structure of the active region of renin while it was occupied by prototype molecule designed by Pfizer chemists.
 Pfizer scientists produced large quantities of the naturally scarce human renin using genetically altered mouse cells. Once purified, the enzyme was flown to London, where researchers from both centers grew crystals of renin in combination with the prototype. The Birkbeck group then fired X-rays through the crystal, and used the diffraction pattern to determine the structure of the molecular complex.
 The new results sharpen scientists' understanding of the highly specific action of renin. Regions of the renin molecule which were not clear in previous images can now be seen with precision, and their functions understood. The exact interactions of the prototype molecule with renin are also seen clearly, thus sharpening the ability of chemists to make new substances which will be highly effective in blocking the renin-angiotensin cascade at its inception.
 The Pfizer authors listed on the paper are: P.M. Hobart, K.F. Geoghegan, M.J. Ammirati, D.E. Danley, B.A. O'Connor and D.J. Hoover.
 Birkbeck College authors are: V. Dhanaraj, C. Dealwis, C. Frazao, M. Badasso, B.L. Sibandam, I.J. Tickle, J.B. Cooper, H.P.C. Driessen, M. Newman, C. Aguilar, S.P. Wood and T.L. Blundell.
 Pfizer Central Research, headquartered in Groton, is the worldwide pharmaceutical, animal health and specialty chemicals research and development organization of Pfizer Inc.
 Pfizer Inc (NYSE: PFE) is a research-based, diversified health care company with global operations. The company reported sales of approximately $6.95 billion for 1991.
 -0- 6/23/92
 /CONTACT: Brian McGlynn of Pfizer, 203-441-5448/
 (PFE) CO: Pfizer Inc ST: Connecticut IN: MTC SU:


PS-CK -- NY043 -- 2851 06/23/92 12:31 EDT
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Date:Jun 23, 1992
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