Prourokinase, also termed single-chain urokinase-type plasminogen acti
vator (scu-PA), is the natural precursor of the two-chain plasminogen
activator urokinase (tcu-PA). Prourokinase was first described in 1973
. The remarkable properties of scu-PA, such as increased fibrinolytic
activity ii treated with plasmin, persistency of its activity in plasm
a, and its ability of fibrin-specific action, raised interest in its u
se as a thrombolytic agent. Since natural sources are not suitable for
commercial exploitation, production of scu-PA requires the use of rec
ombinant gene technology. In contrast to prourokinase from natural sou
rces, scu-PA from recombinant bacteria is unglycosylated and was named
'saruplase'. The protein structure of saruplase complies with that of
natural scu-PA. It consists of a single peptide chain of 411 amino ac
ids (MW: 46344 Da) arranged in three protein domains. Saruplase is con
verted to the fully active two-chain proteinase (tcu-PA) by a single p
eptide cleavage catalyzed, for example, by plasmin. Although structura
lly related, saruplase differs from other plasminogen activators, such
as natural urokinase or tissue-type plasminogen activators, in functi
onally relevant details. It generates plasmin by a positive feedback c
ycle which can be triggered by minute initial activities and may contr
ibute to fast action. It combines properties of a proenzyme and an enz
yme, as it is not inhibited in plasma but appears to be active enough
to trigger plasmin generation. The ability to lyse clots without syste
mic fibrinogen breakdown has been confirmed in various pharmacological
models. The fibrin-selectivity of saruplase must be different from th
at of tissue-type plasminogen activators, since scu-PA does not bind t
o fibrin. This property of scu-PA is explained by its preference for a
ctivation of fibrin-bound over plasmatic plasminogen, probably support
ed by deficient inhibitor capacity at the fibrin clot site. if rapid a
nd complete clot lysis is to be achieved, e.g., in treatment of acute
myocardial infarction (AMI), saruplase doses are required which can le
ad to systemic fibrinogen degradation. This is considered to reflect a
n acceleration of overall plasminogen activation rather than a loss of
saruplase's preference of action. The paradigm of fibrin selectivity
has not met all its claims in practice. There is no proof of a correla
tion between bleeding and fibrinogen decrease. Further, binding to fib
rin may affect the thrombolytic activity of a plasminogen activator, s
ince it prevents penetration into the clot matrix. In conclusion, saru
plase is a recombinant fibrinolytic agent which is related to other pl
asminogen activators, but is unique in its structure and properties. T
his justifies regarding saruplase as a promising modern thrombolytic a
gent.