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
Salivary gland serous fluid and mucus, and enters the oral cavity via the submandibular duct or Wharton duct. Approximately 65-70% of saliva in the oral cavity is produced by the submandibular glands, even though they are much smaller than the parotid glands. This gland can usually be felt via palpation of the neck, as it is in the superficial cervical region and feels like a rounded ball. It is located about two fingers above the Adam's apple (laryngeal prominence) and about two inches apart under the chin. The sublingual glands are a pair of major salivary glands located inferior to the tongue,