Pharmacologically relevant proteins

Abstract The emergence of structure-based drug design as a tool for drug discovery and development has focused increased attention on pharmacologically relevant proteins and the use of their three-dimensional structures to design novel pharmaceutical agents. This review describes recent structural studies of selected macromolecules that have been identified as targets for drug development. Several examples of the successful application of structure-based drug design techniques are also described.

[1]  S E Ealick,et al.  Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[2]  P. Colman Structural basis of antigenic variation: Studies of influenza virus neuraminidase , 1992, Immunology and cell biology.

[3]  S. Nair,et al.  Crystallographic studies of azide binding to human carbonic anhydrase II. , 1993, European journal of biochemistry.

[4]  K. Miyazono,et al.  Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. , 1992, Biochemical and biophysical research communications.

[5]  D. Matthews,et al.  Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones. , 1993, Journal of medicinal chemistry.

[6]  G. Air,et al.  Identification of critical contact residues in the NC41 epitope of a subtype N9 influenza virus neuraminidase , 1993, Proteins.

[7]  Molecular modeling studies in the complex between cyclophilin and cyclosporin A. , 1992, Protein engineering.

[8]  R. Schinazi,et al.  Substrate specificity of Escherichia coli thymidine phosphorylase for pyrimidine nucleosides with anti-human immunodeficiency virus activity. , 1992, Biochemical pharmacology.

[9]  W. Guida,et al.  Structure-based design of inhibitors of purine nucleoside phosphorylase. 1. 9-(arylmethyl) derivatives of 9-deazaguanine. , 1993, Journal of medicinal chemistry.

[10]  S R Jordan,et al.  Design and synthesis of novel 6,7-imidazotetrahydroquinoline inhibitors of thymidylate synthase using iterative protein crystal structure analysis. , 1992, Journal of medicinal chemistry.

[11]  A. Liljas,et al.  Refined structure of the aminobenzolamide complex of human carbonic anhydrase II at 1.9 A and sulphonamide modelling of bovine carbonic anhydrase III. , 1993, International journal of biological macromolecules.

[12]  S. Climie,et al.  Complete replacement set of amino acids at the C-terminus of thymidylate synthase: quantitative structure-activity relationship of mutants of an enzyme. , 1992, Biochemistry.

[13]  W. Cook,et al.  Three-dimensional structure of thymidine phosphorylase from Escherichia coli at 2.8 A resolution. , 1991, The Journal of biological chemistry.

[14]  R. Gilbertsen,et al.  Comparative in vitro and in vivo activities of two 9-deazaguanine analog inhibitors of purine nucleoside phosphorylase, CI-972 and PD 141955. , 1992, Biochemical pharmacology.

[15]  D. Borhani,et al.  The crystal structure of the aldose reductase.NADPH binary complex. , 1992, The Journal of biological chemistry.

[16]  S. Freer,et al.  Design of enzyme inhibitors using iterative protein crystallographic analysis. , 1991, Journal of medicinal chemistry.

[17]  Robert Huber,et al.  The refined 1.9 A crystal structure of human alpha‐thrombin: interaction with D‐Phe‐Pro‐Arg chloromethylketone and significance of the Tyr‐Pro‐Pro‐Trp insertion segment. , 1989 .

[18]  R. Macleod,et al.  Metabolism of 2',3'-dideoxyinosine (ddI) in human blood. , 1992, British journal of clinical pharmacology.

[19]  W G Laver,et al.  Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex. , 1992, Journal of molecular biology.

[20]  Berthold Von Freyberg,et al.  Receptor-induced conformation change of the immunosuppressant cyclosporin A. , 1991, Science.

[21]  R. Webster,et al.  Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface. , 1992, Journal of molecular biology.

[22]  H Brandstetter,et al.  Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics. , 1992, Journal of molecular biology.

[23]  A. Tulinsky,et al.  Structure of the hirulog 3-thrombin complex and nature of the S' subsites of substrates and inhibitors. , 1994, Biochemistry.

[24]  M. Saier,et al.  Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  T. Flynn,et al.  Studies on pig muscle aldose reductase. Kinetic mechanism and evidence for a slow conformational change upon coenzyme binding. , 1992, The Journal of biological chemistry.

[26]  D. Moras,et al.  Novel NADPH-binding domain revealed by the crystal structure of aldose reductase , 1992, Nature.

[27]  R. Stroud,et al.  Cofactor triggers the conformational change in thymidylate synthase: implications for an ordered binding mechanism. , 1992, Biochemistry.

[28]  A. Liljas,et al.  The structure of human carbonic anhydrase II in complex with bromide and azide , 1993, FEBS letters.

[29]  S. Halazy,et al.  Phosphonate derivatives of N9-benzylguanine: a new class of potent purine nucleoside phosphorylase inhibitors , 1992 .

[30]  B. Jonsson,et al.  Importance of the conserved active-site residues Tyr7, Glu106 and Thr199 for the catalytic function of human carbonic anhydrase II. , 1993, European journal of biochemistry.

[31]  C. S. Devine,et al.  Involvement of cysteine residues in catalysis and inhibition of human aldose reductase. Site-directed mutagenesis of Cys-80, -298, and -303. , 1992, The Journal of biological chemistry.

[32]  Y. Thériault,et al.  Solution structure of the cyclosporin A/cyclophilin complex by NMR , 1993, Nature.

[33]  C. Fierke,et al.  Engineering the zinc binding site of human carbonic anhydrase II: structure of the His-94-->Cys apoenzyme in a new crystalline form. , 1993, Biochemistry.

[34]  S. Schreiber,et al.  The conformation of cyclosporin a bound to cyclophilin is altered (once again) following binding to calcineurin: an analysis of receptor-ligand-receptor interactions , 1992 .

[35]  E. Purisima,et al.  Design of a linker for trivalent thrombin inhibitors: interaction of the main chain of the linker with thrombin. , 1993, Biochemistry.

[36]  R. Bicknell,et al.  Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. , 1992, Biochemistry.

[37]  J. Helliwell,et al.  Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution. , 1992, The Journal of biological chemistry.

[38]  J. N. Varghese,et al.  Structure of the catalytic and antigenic sites in influenza virus neuraminidase , 1983, Nature.

[39]  J. Wu,et al.  Metabolism of 4'-azidothymidine. A compound with potent and selective activity against the human immunodeficiency virus. , 1992, The Journal of biological chemistry.

[40]  Victor L. Hsu,et al.  Solution structure of cyclosporin A and a nonimmunosuppressive analog bound to fully deuterated cyclophilin. , 1992, Biochemistry.

[41]  R. Huber,et al.  Impact of protein-protein contacts on the conformation of thrombin-bound hirudin studied by comparison with the nuclear magnetic resonance solution structure of hirudin(1-51). , 1992, Journal of molecular biology.

[42]  D. M. Ryan,et al.  Rational design of potent sialidase-based inhibitors of influenza virus replication , 1993, Nature.

[43]  M. Walkinshaw,et al.  X-ray structure of a decameric cyclophilin-cyclosporin crystal complex , 1993, Nature.

[44]  A. Eriksson,et al.  Refined structure of bovine carbonic anhydrase III at 2.0 Å resolution , 1993, Proteins.

[45]  A. Tulinsky,et al.  The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer. , 1994, The Journal of biological chemistry.

[46]  R M Stroud,et al.  Structural basis for recognition of polyglutamyl folates by thymidylate synthase. , 1992, Biochemistry.

[47]  R M Stroud,et al.  Atomic structure of thymidylate synthase: target for rational drug design. , 1987, Science.

[48]  F A Quiocho,et al.  An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. , 1992, Science.

[49]  J. Feigon,et al.  Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[50]  J. Liu,et al.  Crystal structure of recombinant human T-cell cyclophilin A at 2.5 A resolution. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[51]  P. Colman,et al.  The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor , 1992, Proteins.

[52]  D. Santi,et al.  Mutation of asparagine 229 to aspartate in thymidylate synthase converts the enzyme to a deoxycytidylate methylase. , 1992, Biochemistry.

[53]  N. Dodsworth,et al.  Thymidine phosphorylase activity of platelet-derived endothelial cell growth factor is responsible for endothelial cell mitogenicity. , 1993, European journal of biochemistry.

[54]  A. Yoshimura,et al.  Angiogenic factor , 1992, Nature.

[55]  P. W. Woo,et al.  Inhibitors of human purine nucleoside phosphorylase. Synthesis and biological activities of 8-amino-3-benzylhypoxanthine and related analogues. , 1992, Journal of medicinal chemistry.

[56]  A Tulinsky,et al.  Structures of thrombin complexes with a designed and a natural exosite peptide inhibitor. , 1993, The Journal of biological chemistry.

[57]  K. Waltersson,et al.  The crystal structure of Cs[VOF3] · 12H2O , 1979 .

[58]  A. Liljas,et al.  Crystallographic analysis of Thr‐200 → His human carbonic anhydrase II and its complex with the substrate, HCO  3− , 1993, Proteins.

[59]  K. Bohren,et al.  Catalytic effectiveness of human aldose reductase. Critical role of C-terminal domain. , 1992, The Journal of biological chemistry.

[60]  H. Ke,et al.  Crystal structure of cyclophilin A complexed with substrate Ala-Pro suggests a solvent-assisted mechanism of cis-trans isomerization. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[61]  S. Mangani,et al.  Crystallographic studies of the binding of protonated and unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide and nitrate anions. , 1994, European Journal of Biochemistry.

[62]  S. Schreiber,et al.  Structure-based design of a cyclophilin-calcineurin bridging ligand. , 1993, Science.

[63]  I. Kuntz,et al.  Structure-based discovery of inhibitors of thymidylate synthase. , 1993, Science.

[64]  L. Berliner,et al.  Structural differences in active site-labeled thrombin complexes with hirudin isoinhibitors , 1992, Journal of protein chemistry.

[65]  M. Navia,et al.  Structure-based drug design: applications in immunopharmacology and immunosuppression. , 1993, Trends in pharmacological sciences.

[66]  H. Ke,et al.  Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63 A resolution. , 1992, Journal of molecular biology.

[67]  K. Wüthrich,et al.  Nuclear magnetic resonance solution structure of hirudin(1-51) and comparison with corresponding three-dimensional structures determined using the complete 65-residue hirudin polypeptide chain. , 1992, Journal of molecular biology.

[68]  W L Jorgensen,et al.  Rusting of the lock and key model for protein-ligand binding. , 1991, Science.

[69]  R. Gilbertsen,et al.  Inhibitors of human purine nucleoside phosphorylase. Synthesis of pyrrolo[3,2-d]pyrimidines, a new class of purine nucleoside phosphorylase inhibitors as potentially T-cell selective immunosuppressive agents. Description of 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d] pyrimidin-4-on , 1992, Journal of medicinal chemistry.

[70]  G. Wider,et al.  Cyclosporin A—cyclophilin complex formation A model based on X‐ray and NMR data , 1992, FEBS letters.

[71]  A. Liljas,et al.  Structure of native and apo carbonic anhydrase II and structure of some of its anion-ligand complexes. , 1992, Journal of molecular biology.

[72]  C A Morse,et al.  Crystal-structure-based design and synthesis of benz[cd]indole-containing inhibitors of thymidylate synthase. , 1992, Journal of medicinal chemistry.

[73]  Mark A. Murcko,et al.  Use of structural information in drug design , 1992, Current Biology.

[74]  S. Swaminathan,et al.  A DNA aptamer which binds to and inhibits thrombin exhibits a new structural motif for DNA. , 1993, Biochemistry.

[75]  E. B. Skibo,et al.  Rational design of purine nucleoside phosphorylase inhibitors: Design of 2-(2′-Haloethyl) and 2-ethenyl substituted quinazolinone alkylating agents. , 1992 .