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
Beta-peptide of peptide-based drugs. β-Peptides have been used to mimic natural peptide-based antibiotics such as magainins, which are highly potent but difficult to use as drugs because they are degraded by proteolytic enzymes in the body. 8 beta forms exist: alanine, leucine, lysine, arginine, glutamate, glutamine, phenylalanine, tyrosine forms. Aspartic acid is regarded as both beta and alpha forms, although the beta form is found in microcystins. Beta-peptide β-peptides consist of β amino acids, which have their amino group bonded to the β carbon rather than the α carbon as in the 20 standard biological amino acids. The only common naturally