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
Brunner's glands The duodenum is readily distinguished from other regions of the small intestine by the presence of submucosal Brunner's glands, which may pack the submucosa so completely that the typical submucosal connective tissue is obscured. The Brunner glands, which empty into the intestinal glands, secrete an alkaline fluid composed of mucin, which exerts a physiologic anti-acid function by coating the duodenal epithelium, therefore protecting it from the acid chyme of the stomach. Furthermore, in response to the presence of acid in the duodenum, these glands secrete pepsinogen and urogastrone, which inhibit gastric acid secretion. The main function of these glands is