NONCLINICAL AND CLINICAL CHARACTERIZATION OF A NOVEL ACTING THROMBOLYTIC: ALFIMEPRASE

Abstract

Alfimeprase is a recombinantly produced, truncated form of fibrolase, a known fibrinolytic zinc metalloproteinase that was first isolated from the venom of Agkistrodon contortrix contortrix, the southern copperhead snake (; ). Fibrolase is a member of clan MB of metallopeptidases, family M12, subfamily B (the reprolysins), a grouping of proteolytic enzymes that are comprised of many enzymes originally characterized from snake venoms (). The active site of the molecule was first described by , who identified that the zinc-binding region of the fibrolase molecule spans amino acids 139–159. The alfimeprase molecule differs slightly from native fibrolase where alfimeprase contains 201 amino acids with an N-terminal sequence of SFPQR—in contrast to fibrolase, which is 203 amino acids in length with an N-terminal sequence that begins with EQRFPQR (). These two enzymes are similar with respect to enzymatic activity.