Angiotension

Fig. 10. Pharmacophores for angiotension-converting enzyme. Distances in nm. (a) The stmcture of a semirigid inhibitor and distances between essential atoms from which one pharmacophore was derived (79). (b) In another pharmacophore, atom 1 is a potential zinc ligand (sulfhydryl or carboxylate oxygen), atom 2 is a neutral hydrogen bond acceptor, atom 3 is an anion (deprotonated sulfur or charged oxygen), atom 4 indicates the direction of a hydrogen bond to atom two, and atom 5 is the central atom of a carboxylate, sulfate, or phosphate of which atom 3 is an oxygen, or atom 5 is an unsaturated carbon when atom 3 is a deprotonated sulfur. The angle 1- -2- -3- -4 is —135 to —180° or 135 to 180°, and 1- -2- -3- -5 is —90 to 90°.

The angiotensin converting enzyme (ACE) is a zinc carboxypeptidase that catalyzes the hydrolysis of the decapeptide angiotension I to the the octapeptide... 

SH Kubo, RJ Cody. Clinical pharmacokinetics of the angiotension converting enzyme inhibitors. Clin Pharmacokinet 10 377-391, 1985. 

Another type of antihypertensive agent is a calcium channel blocker. This was discussed under amlodipine (no. 6) in Section 3.6. Finally, angiotension-converting enzyme (ACE) inhibitors are used in severe... 

Fever is common in, and often a sign of, infection irrespective of its cause. Other diseases, which cause fever, are tumours, non-infectious inflammations, endocrine disorders and thrombo-embolic disease. Drugs can cause fever, e.g. angiotension-II-antagonists, ACE inhibitors and phenytoin. 

N-terminal aspartate to form angiotension III,n and degradation of angiotensions II and III can be initiated by removal of the C-terminal phenylalanine by a prolylcarboxypeptidase.0... 

Angiotensin II has a variety of effects. By constricting blood vessels it raises blood pressure, and by stimulating thirst centers in the brain it increases blood volume. Both angiotensins II and III also act on the adrenal gland to promote the synthesis and release of aldosterone. Most of the effects of angiotension II are mediated by 359-residue seven-helix G-protein linked receptors which activate phospholipase C.p q qr Like other steroid hormones aldosterone acts,via mineralocorticoid receptors, to control transcription of a certain set of proteins. The end effect is to increase the transport of Na+ across the renal tubules and back into the blood. Thus, aldosterone acts to decrease the loss of Na+ from the body. It promotes retention of water and raises... 

NOTE Aldosterone production requires the renin-angiotension system Renin is an enzyme secreted by the juxtaglomerular ceils of the kidney in response to decreased arterial blood pressure and blood flow. Renin stimulates conversion of the protein angiotensinogen to angiotensin I which then becomes angiotensin II. Angiotensin II stimulates the synthesis and release of aldosterone by the adrenal cortex. 

We have also tritiated angiotension to determine the rapidity of destruction and the distribution of angiotensin in the body. The destruction must be rapid, because within 30 minutes peptide fragments were recoverable from organs of rats infused with it. I have summarized what we know about the information and destruction of angiotensin in Figure 4. 

To synthesize short peptides, at high volume and low cost, chemist prefer to use the N carboxyanhydrides (NCA) of aminoacids, protected if necessary on the side chain reactive functional groups. This is the case for intermediates of angiotensing converting enzyme peptides such as L-alanyl-L-proline and Ns-(TFA)-L-lysyl-L-proline. 

The synthesis of microginin, an angiotension converting enzyme inhibitory pentapeptide, involves the multiple steps wherein DEPC is used as coupling agent.73 A key component 193 required for the synthesis of microginin is obtained from N-protected amino acid (191) and amine 192. 

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