Multiple binding mode of reversible synthetic thrombin inhibitors. A comparative structural analysis(589 views) Pavone V, De Simone G, Nastri F, Galdiero S, Staiano N, Lombardi A, Pedone C
Affiliations: Ctro. Interuniversitario di R. P. B., Ctro. Stud. Biocristallografia-CNR, University of Napoli Federico II, via Mezzocannone 4, 80134 Napoli, Italy
Dipartimento di Biochimica Mediche, University of Napoli Federico II, via Pansini 5, 80129 Napoli, Italy
References: Abola, E.E., Sussman, J.L., Prilusky, J., Manning, N.O., Protein data bank archives of three-dimensional macromolecular structures (1997) Methods Enzymol., 277, pp. 556-57
Ascenzi, P., Amiconi, G., Bode, W., Bolognesi, M., Coletta, M., Menegatti, E., Proteinase inhibitors from the European Medicinal Leech Hirudo Medicinalis: Structural functional and biomedical aspects (1995) Molec. Aspects. Med., 16, pp. 215-313
Bajusz, S., Barbas, E., Tolnay, P., Szell, E., Bagdy, D., Inhibition of thrombin and trypsin by tripeptide aldehydes (1978) Int. J. Pept. Protein Res., 12, pp. 217-221
Bajusz, S., Szell, E., Bagdy, D., Barbas, E., Horvath, G., Dioszegi, M., Fittler, Z., Szilagyi, G., Highly active and selective anticoagulants. D-Phe-ProArg-H, a free tripeptide aldehyde prone to spontaneous inactivation, and its stable N-methyl derivative D-Me-Phe-Pro-Arg-H (1990) J. Med. Chem., 33, pp. 1729-1735
Balasubramanian, N., Laurent, D.R.S., Federici, M.E., Meanwell, N.A., Wright, J.J., Schumacher, W.A., Seiler, S.M., Active site-directed synthetic thrombin inhibitors: Synthesis, in vitro and in vivo activity profile of BMY 44621 and analogs. An examination of the role of the amino group in the D-Phe-Pro-Arg-H series (1993) J. Med. Chem., 36, pp. 300-303
Banner, D.W., Hadvary, P., Crystallographic analysis at 3.0 Å resolution of the binding to human thrombin of four active site-directed inhibitors (1991) J. Biol. Chem., 266, pp. 20085-20093
Bar-Shavit, R., Kahn, A., Wilner, G.D., Fenton II, J.W., Monocyte chemotaxis stimulation by a specific exosite region in thrombin (1993) Science, 220, pp. 728-731
Betz, A., Hopkins, P.C.R., Le Bonniec, B.F., Stone, S.R., Contribution of interactions with the core domain of hirudin to the stability of its complex with thrombin (1994) Biochem. J., 298, pp. 507-510
Bizios, R., Lai, L., Fenton II, J.W., Malik, A.B., Thrombin-induced chemotaxis and aggregation of neutrophilis (1986) J. Cell. Physiol., 128, pp. 485-490
Bode, W., Huber, R., Natural protein proteincase inhibitors and their interaction with proteinases (1992) Eur. J. Biochem., 204, pp. 443-452
Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S.R., Hofsteenge, J., The refined 1.9 Å crystal structure of human α-thrombin: Interaction with D-Phe-Pro-Arg-chloromethylketone and significance of theTyr-Pro-Pro-Trp insertion segment (1989) EMBO J., 8, pp. 3467-3475
Bode, W., Turk, D., Karshikov, A., The refined 1.9 Å X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human α-thrombin: Structure analysis overall structure electrostatic properties detailed active-site geometry and structure-function relationships (1992) Protein Sci., 1, pp. 426-471
Bouton, M.C., Jandrot-Perrus, M., Bezeaud, A., Guillin, M.C., Late fibrin(ogen) fragment E modulates human α-thrombin specificity (1993) Eur. J. Biochem., 215, pp. 143-149
Brandstetter, H., Turk, D., Hoeffken, H.W., Grosse, D., Stürzebecher, J., Martin, P.D., Ewards, B.F.P., Bode, W., Defined 2.3 Å x-ray crystal structure of bovine thrombin complexes formed with the benzamldine and arginine-based thrombin Inhibitors NAPAP 4-TAPAP and MQPA (1992) J. Mol. Biol., 226, pp. 1085-1099
Chen, L.B., Buchanam, J.M., Mitogenic activity of blood components, I. Thrombin and prothrombin (1975) Proc. Natl. Acad. Sci. USA., 72, pp. 131-135
Chirgadze, N.Y., Sall, D.J., Klimkowski, V.J., Clawson, D.K., Briggs, S.L., Hermann, R., Smith, G.F., Wery, G.P., The crystal structure of human α-thrombin complexed with LY178550, a nonpeptidyl, active site-directed, inhibitor (1997) Protein Sci., 6, pp. 1412-1417
Church, F.C., Pratt, C.W., Noyes, C.M., Kalayanamit, T., Sherrit, G.B., Tobin, R.B., Meade, B., Structural and functional properties of human α-thrombin, phosphopyridoxylated α-thrpnribih and γtthrombin. Identification of lysyl residues in α-thrombin that are critical for heparin and fibrin(ogen) interactions (1989) J. Biol. Chem., 264, pp. 18419-18425
Costanzo, M.J., Maryanoff, B.E., Hecker, L.R., Schott, M.R., Yabut, S.C., Potent thrombin inhibitors that probe the S1′ subsite: Tripeptide transition state analogues based on a heterocycle-activated carbonyl group (1996) J. Med. Chem., 39, pp. 3039-3043
Cunningham, D.D., Farrell, D.H., Thrombin interactions with cultured fibroblasts: Relationship to mitogenic stimulation (1986) Ann. NY Acad. Sci. USA, 485, pp. 240-248
Davie, E.W., Fujikawa, K., Kisiel, W., The coagulation cascade: Initiation, maintenance and regulation (1991) Biochemistry, 30, pp. 10364-10370
De Simone, G., Balliano, G., Milla, P., Gallina, C., Giordano, C., Tarricone, C., Rizzi, M., Ascenzi, P., Human α-thrombin inhibition by the highly selective compounds N-ethoxycarbonyl-D-Phe-Pro-α-azaLys p-nitrophenyl ester: A kinetic, thermodinamic and X-ray crystallographic study (1997) J. Mol. Biol., 269, pp. 558-569
De Simone, G., Lombardi, A., Galdiero, S., Nastri, F., Della Morte, R., Staiano, N., Pedone, C., Pavone, V., Hirunorms are true hirudin mimetics: The crystal structure of human α-thrombin:hirunorm V complex (1998) Protein Sci., 7, pp. 243-253
Di Cera, E., Dand, Q.D., Ayala, Y.M., Molecular mechanism of thrombin function (1997) Cell. Mol. Life Sci., 53, pp. 701-730
Dimaio, J., Gibb, B., Munn, D., Lefebre, J., Ni, F., Konishi, Y., A new class of potent thrombin inhibitors that incorporates a scissile pseudopeptide bond (1991) FEBS Letters, 282, pp. 47-52
Feng, D.-M., Gardell, S.J., Lewis, S.D., Bock, M.G., Chen, Z., Discovery of a novel, selective and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position (1997) J. Med. Chem., 40, pp. 3726-3733
Fenton II, J.W., Thrombin specificity (1988) Ann. NY Acad. Sci., 370, pp. 468-495
Fenton II, J.W., Bing, D.H., Thrombin active-site regions (1986) Semin. Thromb. Haemostasis, 12, pp. 200-208
Fenton II, J.W., Olson, T.A., Zabinski, M.P., Wilner, G.D., Anion binding exosite of human α-thrombin and fibrin(ogen) recognition (1988) Biochemistry, 27, pp. 7106-7112
Fenton II, J.W., Ofosu, F.A., Moon, D.G., Maraganore, J.M., Thrombin structure and function: Why thrombin is the primary target for antithrombotics (1991) Blood Coag: Fibrinol., 2, pp. 69-75
F́thière, J., Tsuda, Y., Coulombe, R., Konishi, Y., Cygler, M., Crystal structure of two new bifunctional nonsubstrate type thrombin inhibitors complexed with human α-thrombin (1996) Protein Sci., 5, pp. 1174-1183
Fevig, J.M., Abelman, M.M., Brittelli, D.R., Kettner, C.A., Knabb, R.M., Weber, P.C., Design and synthesis of ring-costrained boropeptide thrombin inhibitors (1996) Bioorg. Med. Che. Lett., 6, pp. 295-300
Fusetani, N., Matsunaga, S., Matsumoto, H., Takebayashi, Y., Cyclotheonamides, potent thrombin inhibitors, from a marine sponge Theonella sp (1990) J. Am. Chem. Soc., 112, pp. 7053-7054
Gan, Z.-R., Li, Y., Chen, Z., Lewis, S.D., Shafer, J.A., Identification of basic amino acid residues in thrombin essential for heparin-catalyzed inactivatlon by antithrombin III (1994) J. Biol. Chem., 269, pp. 1301-1305
Ganesh, V., Lee, A.Y., Clardy, J., Tulinsky, A., Comparison of the structures of cyclotheonamide A complexes of human α-thrombin arid bovine β-trypsih (1996) Protein Sci., 5, pp. 825-835
Gast, A., Tschopp, T.B., Inhibition of extrinsic and in thrombin generation by a novel synthetic thrombin inhibitor (Ro 46-6240), recombinant hirudin and heparin in human plasma (1995) Blood Coag. Fibrinol., 6, pp. 533-560
Gronke, R.S., Bergman, B.L., Baker, J.B., Thrombin interaction with platelets. Influence of a platelet protease nexin (1987) J. Biol. Chem., 262, pp. 3030-3036
Grütter, M.G., Priestle, J.P., Rahuel, J., Grossenbacher, H., Bode, W., Hofsteenge, J., Stone, S.R., Crystal Structure of the thrombin-hirudin complex: A novel mode of serine proteinase inhibition (1990) EMBO J., 9, pp. 2361-2365
Guillin, M.-C., Bezeaud, A., Bouton, M.-C., Jandrot-Perrus, M., Thrombin specificity (1995) Thromb. and Hemost., 74, pp. 129-133
Haghihara, M., Schreiber, S.L., Reassignment of stereochemistry and total synthesis of the thrombih inhibitor cyclotheonamide B (1992) J. Am. Chem. Soc., 114, pp. 6570-6571
Håkansson, K., Tulinsky, A., Abelman, M.M., Miller, T.A., Vlasuk, G.P., Bergum, P.W., Lim-Wilby, M.S.L., Brunck, T.K., Crystallographic structure of a peptidyl keto acid inhibitor and human α-thrombin (1995) Bioorg. Med. Chem. Lett., 3, pp. 1009-1017
Hoffsteenge, J., Stone, S.R., The effect of thrombomodulin on the cleavage of fibrinogen fragments by thrombin (1987) Eur. J. Biochem., 168, pp. 49-56
Hopfner, K.P., Di Cera, E., Energetics of thrombin-fibrinogen interaction (1992) Biochemistry, 31, pp. 11567-11571
Hortin, G.L., Trimpe, B.L., Allosteric changes in thrombin's activity produced by peptides corresponding to segments of natural inhibitors and substrates (1991) J. Biol. Chem., 266, pp. 6866-6871
Ishihara, H., Connolly, A.J., Zeng, D., Kahn, M.L., Zheng, Y.W., Timmons, C., Tram, T., Coughlin, S.R., Protease-activated receptor 3 is a second thrombin receptor in humans (1997) Nature, 386, pp. 502-505
Iwanowicz, E.J., Lau, W.F., Lin, J., Roberts, D.G.M., Seiler, S.M., Retro-binding tripeptide thrombin active-site inhibitors: Discovery synthesis and molecular modeling (1994) J. Med. Chem., 37, pp. 2122-2124
Jakubowski, J.A., Maraganore, J.M., Inhibition of coagulation and thrombin induced platelet activities by a synthetic dodecapeptide modeled on the carboxy terminus of hirudin (1990) Blood, 75, pp. 399-406
Kettner, C., Shaw, E., DPheProArgCH2Cl: A selective label for thrombin (1979) Thromb. Res., 14, pp. 969-973
Kettner, C., Mersinger, L., Knabb, R., The selective inhibition of thrombin by peptides boroarginine (1990) J. Biol. Chem., 265, pp. 18289-18297
Kikumoto, R., Tamao, Y., Ohkubo, K., Tezuka, T., Tonomura, S., Okamoto, S., Funahara, Y., Hijikata, A., Thrombin inhibitors. 2. Derivatives of Nα-substituted-L-arginine (1980) J. Med. Chem., 23, pp. 830-836
Kimball, S.D., Challenges in the development of orally bioavailable thrombin active site inhibitors (1995) Blood Coagul. Fibrinol., 6, pp. 511-519
Kline, T., Hammond, C., Bourdon, P., Maraganore, J., Hirulog peptides with scissile bond replacements resistant to thrombin cleavage (1991) Biochem. Biophys. Res. Commun., 177, pp. 1049-1055
Krishnan, R., Tulinsky, A., Vlasuk, G.P., Pearson, D., Vallar, P., Bergum, P., Brynck, T.K., Ripka, W.C., Synthesis structure and structure-activity relationships of divalent thrombin inhibitors containing an, α-keto-amide transition state mimetic (1996) Protein Sci, 5, pp. 422-433
Kristenansky, J.L., Mao, S.J.T., Antithrombin properties of C-terminus of hirudin using synthetic unsulfated Nα-acetyl-hirudin 45-65 (1987) FEBS Letters, 211, pp. 10-16
Krstenansky, J.L., Mao, S.J.T., Structure function relationships of the C-terminal functional domain of hirudine and its variants (1991) Blood Coag. Fibrinolysis, 2, pp. 91-96
Laskowski, M., Kato, I., Protein inhibitors of proteinases (1980) Ann. Rew. Biochem., 49, pp. 593-626
Lesk, A.M., Fordham, W.D., Conservation and Variability in the structures of serine proteinases of the chymotrypsin family (1996) J. Mol. Biol., 258, pp. 501-537
Lewis, S.D., Ng, A.S., Baldwin, J.J., Fusetani, N., Naylor, A.M., Shafer, J.A., Inhibition of thrombin and other trypsin-like serine proteinases by cyclotheonamide A (1993) Tromb. Res., 70, pp. 173-190
Lombardi, A., Nastri, F., Della Morte, R., Rossi, A., De Rosa, A., Staiano, N., Pedone, C., Pavone, V., Rational design of true hirudin mimetics: Synthesis and characterization of multisite-directed α-thrombin inhibitors (1996) J. Med. Chem., 39, pp. 2008-2017
Lyle, T.A., Chen, Z., Appleby, S.D., Freidinger, R.M., Gardens, S.J., Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor (1997) Biorg. Med. Chem. Lett., 7, pp. 67-72
Malley, M.F., Tabernero, L., Chang, C.Y., Ohringer, S.L., Roberts, D.G.M., Das, J., Sack, J.S., Crystallographic determination of the structures of human α-thrombin complexed with BMS-186282 and BMS-189090 (1996) Protein Sci., 5, pp. 221-228
Maraganore, J.M., Bourdon, P., Jablonski, J., Ramachandran, K.L., Fenton II, J.W., Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin (1990) Biochemistry, 29, pp. 7095-7101
Markwardt, F., The development of hirudin as.an antithrombotic drug (1994) Thrombosis Res., 74, pp. 1-23
Martin, P.D., Robertson, W., Turk, D., Huber, R., Bode, W., Edwards, B.F.B., The structure of residues 7-16 of the Aα chain of human fibrinogen bound to bovine thrombin at 2.3Å resolution (1992) J. Biol, Chem., 267, pp. 7911-7920
Martin, P.D., Malkowski, M.G., Dimalo, J., Konishi, Y., Ni, F., Edwards, B.F.B., Bovine thrombin complexed with an uncleavable analog of residues 7-19 of fibrinogen Aa: Geometry of the catalytic triad and interactions of the P1′, P2′, and p3′ substrate residues (1996) Biochemistry, 35, pp. 13030-13039
Maryanoff, B.E., Qiu, X., Padmanabhan, K.P., Tulinsky, A., Almond Jr., H.R., Moleoular basis for the inhibition of human α-thrombin by the macrocyclic peptide cyclotheonamide A (1993) Proc. Natl. Acad. Sci., 90, pp. 8048-8052
Mathew, I.I., Padmanabhan, K.-P., Ganesh, V., Tulinsky, A., Isshii, M., Chen, J., Tfek, C.W., Coughlin, S.R., Crystal lographic structures of thrombin complexed with thrombin receptor of peptides: Existence of expected and novel binding modes (1994) Biochemistry, 33, pp. 3266-3279
Mathews, I.I., Padmanabhan, K.P., Tulinsky, A., Saddler, J.E., Structures of a nonadecapeptide of the fifth EGF domain of thrombomodulin complexed with thrombin (1994) Biochemistry, 33, pp. 13547-13552
Matthews, J.H., Krishnan, R., Costanzo, M.J., Maryanoff, B.E., Tulinsky, A., Crystal structures of thrombin with thiazole-containing inhibitors: Probes of the S1′ binding site (1996) Biophys. J., 71, pp. 2830-2839
Muramatsu, R., Komatsu, Y., Nukui, E., Okayama, T., Morikawa, T., Kobashi, K., Hayashi, H., Structure-activity studies on C-terminal hirudin peptides containing sulfated tyrosine resides (1996) Int. J. Pep. Protein Res., 48, pp. 167-173
Nardini, M., Pesce, A., Rizzi, M., Casale, E., Ferraccioli, R., Balliano, G., Milla, P., Bolognesi, M., Human α-thrombin inhibition by the active site titrant Nα-NN-dimethyl-carbamoyl-α-azalysine p-nitrophenyl ester: A comparative kinetic and x-ray crystallographic study (1996) J. Mol. Biol., 258, pp. 851-859
Naski, M.-C., Fenton, J.W., Maraganore, J.M., Olson, S.T., Shafer, J.A., The COOH-terminal domain of hirudin. An exosite-dlrected competitive inhibitor of the action of α-thrombine on fibrinogen (1990) J. Biol. Chem., 265, pp. 13484-13489
Ni, F., Ripoll, D.R., Martin, P.D., Edwards, B.F.P., Solution structure of a platelet receptor peptide bound to bovine α-thrombin (1992) Biochemistry, 31, pp. 11551-11557
Nienaber, V.L., Amparo, E.C., A noncleavable retro-binding peptide that spans the substrate binding cleft of serine proteases. Atomic structure of nazumamide A: Human thrombin (1996) J. A. Chem. Soc., 118, pp. 6807-6810
Nienaber, V.L., Mersinger, L.J., Kettner, C.A., Structure-based understanding of ligand affinity using human thrombin as a model system (1996) Biochemistry, 35, pp. 9690-9699
Noeske-Jungblut, C., Haendler, B., Donner, P., Alagon, A., Possani, L., Schleuning, W.-D., Triabin, a highly potent excite thrombin inhibitor (1995) J. Biol. Chem., 270, pp. 28629-28634
Obst, U., Gramlich, V., Diederich, F., Weber, L., Banner, D.W., Design of novel, nonpeptidic thrombin inhibitors and stature of a thrombin-inhibitor complex (1995) Angew. Chem. Int. Ed. Engl., 34, pp. 1739-1742
Obst, U., Banner, D.W., Gramlich, V., Weber, L., Diederich, F., Molecular recognition at the thrombin active site: Structure-based design and synthesis of potent and selective thrombin inhibitors and the X-ray crystal structures of two thrombin-hinhtbitor complexes (1997) Chem. and Biol., 4, pp. 287-295
Okamoto, S., Kinjo, K., Hijikata, A., Kikumoto, R., Tamao, Y., Ohkubo, K., Tonomura, S., Thrombin inhibitors. 1. Ester derivatives of Nα-(arylsulfonyl)-L-arginine (1980) J. Med. Chem., 23, pp. 827-830
Okamoto, S., Hijikata, A., Kikumoto, R., Tonomura, S., Hara, N., Ninomiya, K., Maruyama, A., Tamao, Y., Potent Inhibition of thrombin by the newly synthesized arginine derivative No 805. the importance of stereostructure of its carboxamide portion (1981) Biochem. Bibphys: Res. Commun., 101, pp. 440-446
Okayama, T., Muramatsu, R., Seki, S., Nukui, E., Hagiwara, M., Hayashi, H., Morikawa, T., Anticoagulant peptides. synthesis, stability and antithrombin activity of hirudin-C-terminal related peptides and their disulfated analog (1996) Chem. Pharm. Bull., 44, pp. 1344-1350
Olson, S.T., Björk, I., Regulation of thrombin by antithrombin and heparin cofactor II (1992) Thrombin Structure and Function, pp. 159-217. , L. J. Berliner, ed. New York: Plenum Press
Owen, T.J., Krstenansky, J.L., Yates, M.T., Mao, S.J.T., N-terminal requirements of small peptide anticoagulants based on hirudin54-65 (1988) J. Med. Chem., 37, pp. 1009-1011
Powers, J.C., Kam, C.-M., Synthetic substrates and Inhibitors of thrombin (1992) Thrombin Structure and Function, pp. 117-158. , L. J. Berliner, ed. New York: Plenum Press
Qiu, X., Yin, M., Padmanabhan, K.P., Krstenansky, J.L., Tulinsky, A., Structures of thrombin complexes with a designed and a natural exosite peptide inhibitor (1993) J. Biol. Chem., 268, pp. 20318-20326
Rehse, P.H., Steinmetzer, T., Li, Y., Konishi, Y., Cygler, M., Crystal structure of a peptidyl pyridinium methyl ketone inhibitor with thrombin (1995) Biochemistry, 34, pp. 11537-11544
Rogers, S.J., Pratt, C.W., Whinna, H.C., Church, F.C., Role of thrombin exosite in inhibition by heparin cofactor II (1992) J. Biol. Chem., 267, pp. 3613-3617
Rosenberg, R.D., Damus, P.S., The purification and mechanism of action of human antithrombin-heparin cofactor (1973) J. Biol. Chem., 248, pp. 6490-6505
Rydel, T.J., Ravichandran, K.G., Tulinsky, A., Bode, W., Huber, R., Roitsch, C., Fenton II, J.W., The structure of a complex of recombinant hirudin and human α-thrombin (1990) Science, 249, pp. 277-280
Rydel, T.J., Tulinsky, A., Bode, W., Huber, R., Refined structure of the hirudin-thrombin complex (1991) J. Mol. Biol., 221, pp. 583-601
Sawyer, R.T., (1986) Leech Biology and Behaviour, 2. , London: Clarendon, Oxford University Press
Schlechter, I., Berger, A., On the size of the active site in proteinases l Papain (1967) Biochem. Biophys. Res. Commun., 27, pp. 157-162
Semple, J.E., Rowley, D.C., Brunck, T.K., Ha-Uong, T., Minami, N.K., Design, synthesis and evolution of a novel, selective, and orally bioavalable class of thrombin inhibitors: P1-arginyl derivatives incorporating P3-P4 lactam sulfonamide moieties (1996) J. Med. Chem., 39, pp. 4531-4536
Sheehan, J.P., Sadler, J.E., Molecular mapping of the heparin binding exosite. of thrombin (1994) Proc. Natl. Acad. Sci. USA, 91, pp. 5518-5522
Skrzypczak-Jankun, E., Carperos, V.E., Ravichandran, K.G., Tulinsky, A., Westbrook, M., Maraganore, J.M., Structure of hirugen and hirulog 1 complexes of α-thrombin (1991) J. Mol. Biol., 221, pp. 1379-1393
Slon-Usakiewicz, J.J., Purisima, E., Tsuda, Y., Sulea, T., Pedyczak, A., Féthière, J., Cygler, M., Konishi, Y., Nonpolar interactions of thrombin S′ subsites with its bivalent inhibitor: Methyl scan of the inhibitor linker (1997) Biochemistry, 36, pp. 13494-13502
Srinivasan, J., Hu, S., Hrabal, R., Zhu, Y., Komives, E.A., Ni, F., Thrombin bound structure of an EGF subdomain from Human thrombomodulin determined by transferred nuclear Ovherauser effects (1994) Biochemistry, 33, pp. 3553-3560
Steiner, V., Knecht, R., Borsen, K.O., Gassmann, E., Stone, S.R., Raschdorf, F., Schlaeppi, J.-M., Maschler, R., Primary structure and function of novel O-glycosylated hirudins from the leech Hirudinaria manillensis (1992) Biochemistry, 31, pp. 2294-2298
Stone, S.R., Maraganore, J.M., Hirudin interactions with thrombin (1992) Thrombin Structure and Function, pp. 219-256. , L. J. Berliner, ed. New York: Plenum Press
Stubbs, M.T., Bode, W., A player of many parts: The spotlight falls on thrombin's structure (1993) Thromb. Res., 69, pp. 1-58
Stubbs, M.T., Oschkinat, H., Mayr, I., Huber, R., Angliker, H., Stone, S.R., Bode, W., The interaction of thrombin with fibrinogen. A structural basis for its specificity (1992) Eur. J. Biochem., 206, pp. 187-195
Suzuki, K., Nishioka, J., Hayashi, T., Localization of thrombomodulin-binding site within human thrombin (1990) J. Biol. Chem., 265, pp. 13263-13267
Tapparelli, C., Metternich, R., Ehrhardt, C., Cook, N.S., Synthetic low molecular weight thrombin inhibitors: Molecular design and pharmacological profile (1993) Trends Pharmacol. Sci., 74, pp. 366-376
Thurieau, C., Simonet, S., Paladino, J., Prost, J.F., Verbeuren, T., Fauchere, J.L., New Nα-guanidiniobenzoyl derivatives of hirudin 54-65 containing stabilized carboxyl or phosphoryl groups on the side chain of phenylalanine-63 (1994) J. Med. Chem., 37, pp. 625-629
Tollefsen, D.M., Feagler, J.R., Majerus, P.W., The binding of thrombin to the surface of human platelets (1974) J. Biol. Chem., 249, pp. 2646-2651
Tollefsen, D.M., Majerus, D.W., Blank, M.K., Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma (1982) J. Biol. Chem., 257, pp. 2162-2169
Tsuda, Y., Cygler, M., Gibbs, B.F., Pedyczac, A., Féthière, J., Yue, S.Y., Konishi, Y., Design of potent bivalent thrombin inhibitors based on hirudin sequence: Incorporation of non-substrate-type active site inhibitors (1994) Biochemistry, 33, pp. 14443-14451
Tucker, T.J., Lumma, W.J., Mulichak, A.M., Chen, Z., Naylor-Olsen, A.M., Lewis, S.D., Lucas, R., Kuo, L.C., Design of highly potent noncovalent thrornbin inhibitors that utilize a novel lipophilic binding pocket in the thrombin active site (1997) J. Med. Chem., 40, pp. 830-832
Jucker, T.J., Lumma, W.J., Lewis, S.D., Gardell, S.J., Lucas, B.J., Baskin, E.P., Woltmann, R., Vacca, J.P., Potent noncovalent thrombin inhibitors that utilize the unique amino acid D-dicyclohexylalanine in the P3 position. Implications on oral bioavailability and antithrombotic efficacy (1997) J. Med. Chem., 40, pp. 1565-1569
Tulinsky, A., Qiu, X., Active site and exosite binding of α-thrombin (1993) Blood Coagul. Fibrinol., 4, pp. 305-312
Van de Locht, A., Lamba, D., Bauer, M., Huber, R., Friedrich, T., Kröger, B., Höffken, W., Bode, W., Two heads are better than one: Crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin (1995) EMBO J., 14, pp. 5149-5157
Van de Locht, A., Stubbs, M.T., Bode, W., Friedrich, T., Bollschweiler, C., Höffken, W., Huber, R., The ornithodorin-thrombin crystal structure a key to the TAP enigma? (1996) EMBO J., 15, pp. 6011-6017
Vitali, J., Martin, P.D., Malkowski, M.D., Robertson, W.D., Lazar, J.B., Winant, R.C., Johnson, P.J., Edwards, B.F.P., The stucture of a complex of bovine α-thrombin and recombinant hirudin at 2.8 A resolution (1992) J. Biol. Chem., 267, pp. 17670-17678
Vu, T.K.H., Wheaton, V.I., Hung, D.T., Charo, I., Coughlin, S.R., Domains specifying thrombin receptor interaction (1991) Nature, 353, pp. 674-677
Vu, T.K.H., Hung, D.T., Wheaton, V.I., Coughlin, S.R., Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation (1991) Cell, 64, pp. 1057-1068
Wallis, R.B., Hirudins and the role of thrombin: Lessons from leaches (1988) Trends Pharm. Sci., 9, pp. 425-427
Walsmann, P., Markwardt, F., Biochemische and pharmakologische Aspekte des Thrombininhibitors Hirudin (1981) Pharmazie, 36, pp. 653-660
Walsmann, P., Über den Einsatz des spezifischen Thrombininhibitors Hirudin für diagnostische and biochemische Untersuchungen (1988) Pharmazie, 43, pp. 737-744
Weber, P.C., Lee, S.-L., Lewandowski, F.A., Schadt, M.C., Chang, C.-H., Kettner, C.A., Kinetic and crystallographic studies of thrombin with Ac-(D)Phe-Pro-boroArgOH and its lysine, amidine, homolysine and ornitine analogs (1995) Biochemistry, 34, pp. 3750-3757
Zdanov, A., Wu, S., Dimaio, J., Konishi, Y., Li, Y., Wu, X., Edwards, B.F.P., Cygler, M., Crystal structure of the complex of human α-thrombin and nonhydrolyzable bifunctional inhibitors hirutonin-2 and hirutonin-6 (1993) Proteins: Struc. Funct. Genet., 17, pp. 252-265
Abola, E. E., Sussman, J. L., Prilusky, J., Manning, N. O., Protein data bank archives of three-dimensional macromolecular structures (1997) Methods Enzymol., 277, pp. 556-57
Banner, D. W., Hadvary, P., Crystallographic analysis at 3. 0 resolution of the binding to human thrombin of four active site-directed inhibitors (1991) J. Biol. Chem., 266, pp. 20085-20093
Bouton, M. C., Jandrot-Perrus, M., Bezeaud, A., Guillin, M. C., Late fibrin (ogen) fragment E modulates human -thrombin specificity (1993) Eur. J. Biochem., 215, pp. 143-149
Chen, L. B., Buchanam, J. M., Mitogenic activity of blood components, I. Thrombin and prothrombin (1975) Proc. Natl. Acad. Sci. USA., 72, pp. 131-135
Chirgadze, N. Y., Sall, D. J., Klimkowski, V. J., Clawson, D. K., Briggs, S. L., Hermann, R., Smith, G. F., Wery, G. P., The crystal structure of human -thrombin complexed with LY178550, a nonpeptidyl, active site-directed, inhibitor (1997) Protein Sci., 6, pp. 1412-1417
Church, F. C., Pratt, C. W., Noyes, C. M., Kalayanamit, T., Sherrit, G. B., Tobin, R. B., Meade, B., Structural and functional properties of human -thrombin, phosphopyridoxylated -thrpnribih and tthrombin. Identification of lysyl residues in -thrombin that are critical for heparin and fibrin (ogen) interactions (1989) J. Biol. Chem., 264, pp. 18419-18425
Costanzo, M. J., Maryanoff, B. E., Hecker, L. R., Schott, M. R., Yabut, S. C., Potent thrombin inhibitors that probe the S1 subsite: Tripeptide transition state analogues based on a heterocycle-activated carbonyl group (1996) J. Med. Chem., 39, pp. 3039-3043
Cunningham, D. D., Farrell, D. H., Thrombin interactions with cultured fibroblasts: Relationship to mitogenic stimulation (1986) Ann. NY Acad. Sci. USA, 485, pp. 240-248
Davie, E. W., Fujikawa, K., Kisiel, W., The coagulation cascade: Initiation, maintenance and regulation (1991) Biochemistry, 30, pp. 10364-10370
Feng, D. -M., Gardell, S. J., Lewis, S. D., Bock, M. G., Chen, Z., Discovery of a novel, selective and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position (1997) J. Med. Chem., 40, pp. 3726-3733
Fenton II, J. W., Thrombin specificity (1988) Ann. NY Acad. Sci., 370, pp. 468-495
Fenton II, J. W., Bing, D. H., Thrombin active-site regions (1986) Semin. Thromb. Haemostasis, 12, pp. 200-208
Fenton II, J. W., Olson, T. A., Zabinski, M. P., Wilner, G. D., Anion binding exosite of human -thrombin and fibrin (ogen) recognition (1988) Biochemistry, 27, pp. 7106-7112
F thi re, J., Tsuda, Y., Coulombe, R., Konishi, Y., Cygler, M., Crystal structure of two new bifunctional nonsubstrate type thrombin inhibitors complexed with human -thrombin (1996) Protein Sci., 5, pp. 1174-1183
Fevig, J. M., Abelman, M. M., Brittelli, D. R., Kettner, C. A., Knabb, R. M., Weber, P. C., Design and synthesis of ring-costrained boropeptide thrombin inhibitors (1996) Bioorg. Med. Che. Lett., 6, pp. 295-300
Gan, Z. -R., Li, Y., Chen, Z., Lewis, S. D., Shafer, J. A., Identification of basic amino acid residues in thrombin essential for heparin-catalyzed inactivatlon by antithrombin III (1994) J. Biol. Chem., 269, pp. 1301-1305
Gronke, R. S., Bergman, B. L., Baker, J. B., Thrombin interaction with platelets. Influence of a platelet protease nexin (1987) J. Biol. Chem., 262, pp. 3030-3036
Gr tter, M. G., Priestle, J. P., Rahuel, J., Grossenbacher, H., Bode, W., Hofsteenge, J., Stone, S. R., Crystal Structure of the thrombin-hirudin complex: A novel mode of serine proteinase inhibition (1990) EMBO J., 9, pp. 2361-2365
Guillin, M. -C., Bezeaud, A., Bouton, M. -C., Jandrot-Perrus, M., Thrombin specificity (1995) Thromb. and Hemost., 74, pp. 129-133
H kansson, K., Tulinsky, A., Abelman, M. M., Miller, T. A., Vlasuk, G. P., Bergum, P. W., Lim-Wilby, M. S. L., Brunck, T. K., Crystallographic structure of a peptidyl keto acid inhibitor and human -thrombin (1995) Bioorg. Med. Chem. Lett., 3, pp. 1009-1017
Hopfner, K. P., Di Cera, E., Energetics of thrombin-fibrinogen interaction (1992) Biochemistry, 31, pp. 11567-11571
Hortin, G. L., Trimpe, B. L., Allosteric changes in thrombin's activity produced by peptides corresponding to segments of natural inhibitors and substrates (1991) J. Biol. Chem., 266, pp. 6866-6871
Iwanowicz, E. J., Lau, W. F., Lin, J., Roberts, D. G. M., Seiler, S. M., Retro-binding tripeptide thrombin active-site inhibitors: Discovery synthesis and molecular modeling (1994) J. Med. Chem., 37, pp. 2122-2124
Jakubowski, J. A., Maraganore, J. M., Inhibition of coagulation and thrombin induced platelet activities by a synthetic dodecapeptide modeled on the carboxy terminus of hirudin (1990) Blood, 75, pp. 399-406
Kimball, S. D., Challenges in the development of orally bioavailable thrombin active site inhibitors (1995) Blood Coagul. Fibrinol., 6, pp. 511-519
Kristenansky, J. L., Mao, S. J. T., Antithrombin properties of C-terminus of hirudin using synthetic unsulfated N -acetyl-hirudin 45-65 (1987) FEBS Letters, 211, pp. 10-16
Krstenansky, J. L., Mao, S. J. T., Structure function relationships of the C-terminal functional domain of hirudine and its variants (1991) Blood Coag. Fibrinolysis, 2, pp. 91-96
Lesk, A. M., Fordham, W. D., Conservation and Variability in the structures of serine proteinases of the chymotrypsin family (1996) J. Mol. Biol., 258, pp. 501-537
Lewis, S. D., Ng, A. S., Baldwin, J. J., Fusetani, N., Naylor, A. M., Shafer, J. A., Inhibition of thrombin and other trypsin-like serine proteinases by cyclotheonamide A (1993) Tromb. Res., 70, pp. 173-190
Lyle, T. A., Chen, Z., Appleby, S. D., Freidinger, R. M., Gardens, S. J., Synthesis, evaluation, and crystallographic analysis of L-371, 912: A potent and selective active-site thrombin inhibitor (1997) Biorg. Med. Chem. Lett., 7, pp. 67-72
Malley, M. F., Tabernero, L., Chang, C. Y., Ohringer, S. L., Roberts, D. G. M., Das, J., Sack, J. S., Crystallographic determination of the structures of human -thrombin complexed with BMS-186282 and BMS-189090 (1996) Protein Sci., 5, pp. 221-228
Maraganore, J. M., Bourdon, P., Jablonski, J., Ramachandran, K. L., Fenton II, J. W., Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin (1990) Biochemistry, 29, pp. 7095-7101
Martin, P. D., Robertson, W., Turk, D., Huber, R., Bode, W., Edwards, B. F. B., The structure of residues 7-16 of the A chain of human fibrinogen bound to bovine thrombin at 2. 3 resolution (1992) J. Biol, Chem., 267, pp. 7911-7920
Martin, P. D., Malkowski, M. G., Dimalo, J., Konishi, Y., Ni, F., Edwards, B. F. B., Bovine thrombin complexed with an uncleavable analog of residues 7-19 of fibrinogen Aa: Geometry of the catalytic triad and interactions of the P1, P2, and p3 substrate residues (1996) Biochemistry, 35, pp. 13030-13039
Maryanoff, B. E., Qiu, X., Padmanabhan, K. P., Tulinsky, A., Almond Jr., H. R., Moleoular basis for the inhibition of human -thrombin by the macrocyclic peptide cyclotheonamide A (1993) Proc. Natl. Acad. Sci., 90, pp. 8048-8052
Mathew, I. I., Padmanabhan, K. -P., Ganesh, V., Tulinsky, A., Isshii, M., Chen, J., Tfek, C. W., Coughlin, S. R., Crystal lographic structures of thrombin complexed with thrombin receptor of peptides: Existence of expected and novel binding modes (1994) Biochemistry, 33, pp. 3266-3279
Mathews, I. I., Padmanabhan, K. P., Tulinsky, A., Saddler, J. E., Structures of a nonadecapeptide of the fifth EGF domain of thrombomodulin complexed with thrombin (1994) Biochemistry, 33, pp. 13547-13552
Matthews, J. H., Krishnan, R., Costanzo, M. J., Maryanoff, B. E., Tulinsky, A., Crystal structures of thrombin with thiazole-containing inhibitors: Probes of the S1 binding site (1996) Biophys. J., 71, pp. 2830-2839
Naski, M. -C., Fenton, J. W., Maraganore, J. M., Olson, S. T., Shafer, J. A., The COOH-terminal domain of hirudin. An exosite-dlrected competitive inhibitor of the action of -thrombine on fibrinogen (1990) J. Biol. Chem., 265, pp. 13484-13489
Ni, F., Ripoll, D. R., Martin, P. D., Edwards, B. F. P., Solution structure of a platelet receptor peptide bound to bovine -thrombin (1992) Biochemistry, 31, pp. 11551-11557
Nienaber, V. L., Amparo, E. C., A noncleavable retro-binding peptide that spans the substrate binding cleft of serine proteases. Atomic structure of nazumamide A: Human thrombin (1996) J. A. Chem. Soc., 118, pp. 6807-6810
Nienaber, V. L., Mersinger, L. J., Kettner, C. A., Structure-based understanding of ligand affinity using human thrombin as a model system (1996) Biochemistry, 35, pp. 9690-9699
Olson, S. T., Bj rk, I., Regulation of thrombin by antithrombin and heparin cofactor II (1992) Thrombin Structure and Function, pp. 159-217. , L. J. Berliner, ed. New York: Plenum Press
Owen, T. J., Krstenansky, J. L., Yates, M. T., Mao, S. J. T., N-terminal requirements of small peptide anticoagulants based on hirudin54-65 (1988) J. Med. Chem., 37, pp. 1009-1011
Powers, J. C., Kam, C. -M., Synthetic substrates and Inhibitors of thrombin (1992) Thrombin Structure and Function, pp. 117-158. , L. J. Berliner, ed. New York: Plenum Press
Rehse, P. H., Steinmetzer, T., Li, Y., Konishi, Y., Cygler, M., Crystal structure of a peptidyl pyridinium methyl ketone inhibitor with thrombin (1995) Biochemistry, 34, pp. 11537-11544
Rogers, S. J., Pratt, C. W., Whinna, H. C., Church, F. C., Role of thrombin exosite in inhibition by heparin cofactor II (1992) J. Biol. Chem., 267, pp. 3613-3617
Rosenberg, R. D., Damus, P. S., The purification and mechanism of action of human antithrombin-heparin cofactor (1973) J. Biol. Chem., 248, pp. 6490-6505
Rydel, T. J., Ravichandran, K. G., Tulinsky, A., Bode, W., Huber, R., Roitsch, C., Fenton II, J. W., The structure of a complex of recombinant hirudin and human -thrombin (1990) Science, 249, pp. 277-280
Rydel, T. J., Tulinsky, A., Bode, W., Huber, R., Refined structure of the hirudin-thrombin complex (1991) J. Mol. Biol., 221, pp. 583-601
Sawyer, R. T., (1986) Leech Biology and Behaviour, 2. , London: Clarendon, Oxford University Press
Semple, J. E., Rowley, D. C., Brunck, T. K., Ha-Uong, T., Minami, N. K., Design, synthesis and evolution of a novel, selective, and orally bioavalable class of thrombin inhibitors: P1-arginyl derivatives incorporating P3-P4 lactam sulfonamide moieties (1996) J. Med. Chem., 39, pp. 4531-4536
Sheehan, J. P., Sadler, J. E., Molecular mapping of the heparin binding exosite. of thrombin (1994) Proc. Natl. Acad. Sci. USA, 91, pp. 5518-5522
Shuman, R. T., Rothenberger, R. B., Campbell, C. S., Smith, G. F., Gifford-Moore, D. S., Gesellchen, P. D., Highly selective tripeptide thrombin inhibitors (1993) J. Med. Chem., 36, pp. 314-319
Stone, S. R., Maraganore, J. M., Hirudin interactions with thrombin (1992) Thrombin Structure and Function, pp. 219-256. , L. J. Berliner, ed. New York: Plenum Press
Stubbs, M. T., Bode, W., A player of many parts: The spotlight falls on thrombin's structure (1993) Thromb. Res., 69, pp. 1-58
Stubbs, M. T., Oschkinat, H., Mayr, I., Huber, R., Angliker, H., Stone, S. R., Bode, W., The interaction of thrombin with fibrinogen. A structural basis for its specificity (1992) Eur. J. Biochem., 206, pp. 187-195
Tollefsen, D. M., Feagler, J. R., Majerus, P. W., The binding of thrombin to the surface of human platelets (1974) J. Biol. Chem., 249, pp. 2646-2651
Tollefsen, D. M., Majerus, D. W., Blank, M. K., Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma (1982) J. Biol. Chem., 257, pp. 2162-2169
Tucker, T. J., Lumma, W. J., Mulichak, A. M., Chen, Z., Naylor-Olsen, A. M., Lewis, S. D., Lucas, R., Kuo, L. C., Design of highly potent noncovalent thrornbin inhibitors that utilize a novel lipophilic binding pocket in the thrombin active site (1997) J. Med. Chem., 40, pp. 830-832
Jucker, T. J., Lumma, W. J., Lewis, S. D., Gardell, S. J., Lucas, B. J., Baskin, E. P., Woltmann, R., Vacca, J. P., Potent noncovalent thrombin inhibitors that utilize the unique amino acid D-dicyclohexylalanine in the P3 position. Implications on oral bioavailability and antithrombotic efficacy (1997) J. Med. Chem., 40, pp. 1565-1569
Vu, T. K. H., Wheaton, V. I., Hung, D. T., Charo, I., Coughlin, S. R., Domains specifying thrombin receptor interaction (1991) Nature, 353, pp. 674-677
Vu, T. K. H., Hung, D. T., Wheaton, V. I., Coughlin, S. R., Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation (1991) Cell, 64, pp. 1057-1068
Wallis, R. B., Hirudins and the role of thrombin: Lessons from leaches (1988) Trends Pharm. Sci., 9, pp. 425-427
Walsmann, P., ber den Einsatz des spezifischen Thrombininhibitors Hirudin f r diagnostische and biochemische Untersuchungen (1988) Pharmazie, 43, pp. 737-744
Weber, P. C., Lee, S. -L., Lewandowski, F. A., Schadt, M. C., Chang, C. -H., Kettner, C. A., Kinetic and crystallographic studies of thrombin with Ac- (D) Phe-Pro-boroArgOH and its lysine, amidine, homolysine and ornitine analogs (1995) Biochemistry, 34, pp. 3750-3757
Multiple binding mode of reversible synthetic thrombin inhibitors. A comparative structural analysis
The central role of the serine protease thrombin in hemostasis and thrombosis brought many scientists to develop highly potent and selective thrombin inhibitors. Thrombin-inhibitor complexes have extensively been studied in order to understand structure-function relationships, and to design new inhibitors that can be used with broader efficacy over existing antithrombotic agents. In this paper, we summarize in a comparative manner the state of the art on reversible thrombin inhibitors and we discuss some structural aspects of thrombin-inhibitor interaction, which account for the different affinity and potency of these molecules. We also report here our approach to develop a new class of synthetic, multisite-directed thrombin inhibitors, named hirunorms, designed to mimic the distinctive binding mode of hirudin, We emphasize here that, despite the high specificity of thrombin action, the interaction of inhibitors in its active site may occur with quite different mechanisms.
Multiple binding mode of reversible synthetic thrombin inhibitors. A comparative structural analysis
No results.
Multiple binding mode of reversible synthetic thrombin inhibitors. A comparative structural analysis