Discovery and development of direct thrombin inhibitors the binding site for the globular amino-terminal domain and exosite 1 is the binding site for the acidic carboxy-terminal domain of hirudin. Native hirudin, a 65-amino-acid polypeptide, is produced in the parapharyngeal glands of medicinal leeches. Hirudins today are produced by recombinant biotechnology using yeast. These recombinant hirudins lack a sulfate group at Tyr-63 and are therefore called desulfatohirudins. They have a 10-fold lower binding affinity to thrombin compared to native hirudin, but remain a highly specific inhibitor of thrombin and have an inhibition constant for thrombin in the picomolar range. Renal clearance and degradation account for the most part
Renin inhibitor normal conditions, stimulation of the RAAS occurs in response to threats that compromise blood pressure stability, such as hypotension, blood loss and excessive loss of sodium and water. Blood pressure depends on total peripheral resistance and cardiac output. The highly selective aspartic protease renin is secreted from the juxtaglomerular apparatus, which is the only source of active renin, although its precursor, prorenin, can be secreted by other tissues, such as the salivary glands, brain, heart and blood vessels. Renin is a circulating enzyme that acts on a circulating peptide, angiotensinogen. Renin cleaves the peptide at the Leu10–Val11 bond, and this