TAFIa inhibiting nanobodies as profibrinolytic tools and discovery of a new TAFIa conformation

Journal of Thrombosis and Haemostasis

Volumn 9, Issue 11, 2011, Pages 2268-2277

  Hendrickx, M L V ^a   De Winter, A ^a   Buelens, K ^a   Compernolle, G ^a   Hassanzadeh Ghassabeh, G ^b,c   Muyldermans, S ^b,c   Gils, A ^a   Declerck, P J ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^c DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

Author keywords

Activated thrombin activatable fibrinolysis inhibitor; Fibrinolysis; Nanobody

Indexed keywords

NANOPARTICLE; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR A147; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR C305; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR I325; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR I329; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR Q335; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR Y333; THROMBOMODULIN; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG BINDING SITE; DRUG CONFORMATION; FIBRINOLYSIS; HUMAN; IC 50; IN VITRO STUDY; PRIORITY JOURNAL;

ANTIBODIES; CARBOXYPEPTIDASE U; FIBRINOLYSIS; FIBRINOLYTIC AGENTS; HUMANS; MUTANT PROTEINS; PEPTIDE LIBRARY; PROTEIN CONFORMATION;

EID: 80055102661     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2011.04495.x     Document Type: Article

References (32)

1. Fleury V, Angles-Cano E. Characterization of the binding of plasminogen to fibrin surfaces: the role of carboxy-terminal lysines. Biochemistry 1991; 30: 7630-8.
2. Hendriks D, Scharpe S, van Sande M, Lommaert MP. Characterisation of a carboxypeptidase in human serum distinct from carboxypeptidase N. J Clin Chem Clin Biochem 1989; 27: 277-85.
3. Eaton DL, Malloy BE, Tsai SP, Henzel W, Drayna D. Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. J Biol Chem 1991; 266: 21833-8.
4. Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. J Biol Chem 1995; 270: 14477-84.
5. Wang W, Boffa MB, Bajzar L, Walker JB, Nesheim ME. A study of the mechanism of inhibition of fibrinolysis by activated thrombin-activable fibrinolysis inhibitor. J Biol Chem 1998; 273: 27176-81.
6. Schatteman KA, Goossens FJ, Scharpe SS, Hendriks DF. Proteolytic activation of purified human procarboxypeptidase U. Clin Chim Acta 2000; 292: 25-40.
7. Boffa MB, Bell R, Stevens WK, Nesheim ME. Roles of thermal instability and proteolytic cleavage in regulation of activated thrombin-activable fibrinolysis inhibitor. J Biol Chem 2000; 275: 12868-78.
8. Boffa MB, Wang W, Bajzar L, Nesheim ME. Plasma and recombinant thrombin-activable fibrinolysis inhibitor (TAFI) and activated TAFI compared with respect to glycosylation, thrombin/thrombomodulin-dependent activation, thermal stability, and enzymatic properties. J Biol Chem 1998; 273: 2127-35.
9. Marx PF, Hackeng TM, Dawson PE, Griffin JH, Meijers JC, Bouma BN. Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage. J Biol Chem 2000; 275: 12410-5.
10. Wang YX, da Cunha V, Vincelette J, Zhao L, Nagashima M, Kawai K, Yuan S, Emayan K, Islam I, Hosoya J, Sullivan ME, Dole WP, Morser J, Buckman BO, Vergona R. A novel inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa) - part II: enhancement of both exogenous and endogenous fibrinolysis in animal models of thrombosis. Thromb Haemost 2007; 97: 54-61.
11. Schneider M, Boffa M, Stewart R, Rahman M, Koschinsky M, Nesheim M. Two naturally occurring variants of TAFI (Thr-325 and Ile-325) differ substantially with respect to thermal stability and antifibrinolytic activity of the enzyme. J Biol Chem 2002; 277: 1021-30.
12. Ceresa E, Peeters M, Declerck PJ, Gils A. Announcing a TAFIa mutant with a 180-fold increased half-life and concomitantly a strongly increased antifibrinolytic potential. J Thromb Haemost 2007; 5: 418-20.
13. Willemse JL, Heylen E, Nesheim ME, Hendriks DF. Carboxypeptidase U (TAFIa): a new drug target for fibrinolytic therapy? J Thromb Haemost 2009; 7: 1962-71.
14. Hillmayer K, Vancraenenbroeck R, De Maeyer M, Compernolle G, Declerck PJ, Gils A. Discovery of novel mechanisms and molecular targets for the inhibition of activated thrombin activatable fibrinolysis inhibitor. J Thromb Haemost 2008; 6: 1892-9.
15. Gils A, Ceresa E, Macovei AM, Marx PF, Peeters M, Compernolle G, Declerck PJ. Modulation of TAFI function through different pathways - implications for the development of TAFI inhibitors. J Thromb Haemost 2005; 3: 2745-53.
16. Bajzar L, Nesheim ME, Tracy PB. The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood 1996; 88: 2093-100.
17. Walker JB, Hughes B, James I, Haddock P, Kluft C, Bajzar L. Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro. J Biol Chem 2003; 278: 8913-21.
18. Schneider M, Nesheim M. Reversible inhibitors of TAFIa can both promote and inhibit fibrinolysis. J Thromb Haemost 2003; 1: 147-54.
19. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, Songa EB, Bendahman N, Hamers R. Naturally occurring antibodies devoid of light chains. Nature 1993; 363: 446-8.
20. Muyldermans S, Atarhouch T, Saldanha J, Barbosa JA, Hamers R. Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains. Protein Eng 1994; 7: 1129-35.
21. Lauwereys M, Arbabi Ghahroudi M, Desmyter A, Kinne J, Holzer W, De Genst E, Wyns L, Muyldermans S. Potent enzyme inhibitors derived from dromedary heavy-chain antibodies. EMBO J 1998; 17: 3512-20.
22. Conrath KE, Lauwereys M, Galleni M, Matagne A, Frere JM, Kinne J, Wyns L, Muyldermans S. Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae. Antimicrob Agents Chemother 2001; 45: 2807-12.
23. Buelens K, Hassanzadeh-Ghassabeh G, Muyldermans S, Gils A, Declerck PJ. Generation and characterization of inhibitory nanobodies towards thrombin activatable fibrinolysis inhibitor. J Thromb Haemost 2010; 8: 1302-12.
24. Ceresa E, van de Borne K, Peeters M, Lijnen HR, Declerck PJ, Gils A. Generation of a stable activated thrombin activable fibrinolysis inhibitor variant. J Biol Chem 2006; 281: 15878-83.
25. Develter J, Booth NA, Declerck PJ, Gils A. Bispecific targeting of thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 by a heterodimer diabody. J Thromb Haemost 2008; 6: 1884-91.
26. De Genst E, Silence K, Ghahroudi MA, Decanniere K, Loris R, Kinne J, Wyns L, Muyldermans S. Strong in vivo maturation compensates for structurally restricted H3 loops in antibody repertoires. J Biol Chem 2005; 280: 14114-21.
27. Khan IA, Gowda RM. Clinical perspectives and therapeutics of thrombolysis. Int J Cardiol 2003; 91: 115-27.
28. Nagashima M, Werner M, Wang M, Zhao L, Light DR, Pagila R, Morser J, Verhallen P. An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model. Thromb Res 2000; 98: 333-42.
29. Pereira Arias-Bouda LM, Kuijper S, van Deutekom H, van Gijlswijk R, Pekel I, Jansen HM, Kolk AH. Enzyme-linked immunosorbent assays using immune complexes for the diagnosis of tuberculosis. J Immunol Methods 2003; 283: 115-24.
30. Leurs J, Nerme V, Sim Y, Hendriks D. Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold-dependent mechanism. J Thromb Haemost 2004; 2: 416-23.
31. Walker JB, Bajzar L. The intrinsic threshold of the fibrinolytic system is modulated by basic carboxypeptidases, but the magnitude of the antifibrinolytic effect of activated thrombin-activable fibrinolysis inhibitor is masked by its instability. J Biol Chem 2004; 279: 27896-904.
32. Marx PF, Plug T, Havik SR, Morgelin M, Meijers JC. The activation peptide of thrombin-activatable fibrinolysis inhibitor: a role in activity and stability of the enzyme? J Thromb Haemost 2009; 7: 445-52.