Prolyl peptidases: A serine protease subfamily with high potential for drug discovery

Current Opinion in Chemical Biology

Volumn 7, Issue 4, 2003, Pages 496-504

  Rosenblum, Jonathan S ^a   Kozarich, John W ^a  

^a ACTIVX BIOSCIENCES INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 [[2 [[2 (2 CYANO 1 PYRROLIDINYL) 2 OXOETHYL]AMINO]ETHYL]AMINO]NICOTINONITRILE; ACYLAMINO ACID RELEASING ENZYME; ADENOSINE DEAMINASE; AMINO ACID DERIVATIVE; ANTINEOPLASTIC AGENT; CD 26; CD45 ANTIGEN; DIPEPTIDASE; DIPEPTIDYL PEPTIDASE; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; FIBROBLAST ACTIVATION PROTEIN ANTIBODY; ISOLEUCINE THIAZOLIDIDE; LITHIUM; M PROTEIN; NOOTROPIC AGENT; PEPTIDE; PEPTIDE HORMONE; PLACEBO; PROLINE; PROLINE CARBOXYPEPTIDASE; PROLINE DIPEPTIDASE; PROLINE IMINOPEPTIDASE; PROLINE OLIGOPEPTIDASE INHIBITOR; PROLYL ENDOPEPTIDASE; PROTEIN DERIVATIVE; PROTEIN INHIBITOR; QUIESCENT CELL PROLINE DIPEPTIDASE; SEPRASE; SERINE PROTEINASE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALYLBOROPROLINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANEMIA; APOPTOSIS; CARCINOGENESIS; CELL COMPARTMENTALIZATION; CLINICAL TRIAL; COGNITION; DEMENTIA; DIABETES MELLITUS; DISEASE ASSOCIATION; DOWN SYNDROME; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; DRUG SENSITIVITY; DRUG TARGETING; DRUG TOLERABILITY; ENZYME ACTIVITY; GENE DUPLICATION; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; MALIGNANT NEOPLASTIC DISEASE; MEMBRANE; MULTIPLE SCLEROSIS; NEUTROPENIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; PROTEIN TARGETING; REGULATORY MECHANISM; REVIEW; RHEUMATOID ARTHRITIS; T LYMPHOCYTE ACTIVATION; TISSUE DISTRIBUTION; TREATMENT INDICATION;

EID: 0043073112     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(03)00084-X     Document Type: Review

References (70)

1. Barrett AJ, Rawlings ND, Woessner JF (Eds): Handbook of Proteolytic Enzymes. San Diego: Academic Press; 1998.
2. de Meester I., Lambeir A.M., Proost P., Scharpe S. Dipeptidyl peptidase IV substrates. An update on in vitro peptide hydrolysis by human DPPIV. Adv. Exp. Med. Biol. 524:2003;3-17.
3. Lambeir A.M., Proost P., Durinx C., Bal G., Senten K., Augustyns K., Scharpe S., Van Damme J., De Meester I. Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family. J. Biol. Chem. 276:2001;29839-29845.
4. Ludwig A., Schiemann F., Mentlein R., Lindner B., Brandt E. Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I-TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine. J. Leukoc. Biol. 72:2002;183-191.
5. Proost P., Schutyser E., Menten P., Struyf S., Wuyts A., Opdenakker G., Detheux M., Parmentier M., Durinx C., Lambeir A.M.et al. Amino-terminal truncation of CXCR3 agonists impairs receptor signaling and lymphocyte chemotaxis, while preserving antiangiogenic properties. Blood. 98:2001;3554-3561.
6. Mentlein R., Schiemann F., Ludwig A., Brandt E. Modification of the biological activity of chemokines by dipeptidyl peptidase IV-a side effect in the use of inhibitors? Adv. Exp. Med. Biol. 524:2003;37-47.
7. Zhu L., Tamvakopoulos C., Xie D., Dragovic J., Shen X., Fenyk-Melody J.E., Schmidt K., Bagchi A., Griffin P.R., Thornberry N.A.et al. The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: in vivo metabolism of pituitary adenylate cyclase activating polypeptide. [1-38]. J. Biol. Chem. 278:2003;22418-22423 The authors have established a rapid, sensitive kinetic method that hold the promise of providing quantitative analysis of peptide hormone hydrolysis by enzymes at concentrations that are relevant to those found in plasma.
8. Hiramatsu H., Kyono K., Higashiyama Y., Fukushima C., Shima H., Sugiyama S., Inaka K., Yamamoto A., Shimizu R. The structure and function of human dipeptidyl peptidase IV, possessing a unique eight-bladed beta-propeller fold. Biochem. Biophys. Res. Commun. 302:2003;849-854.
9. ••] provide the first view of the overall structure of DPP IV, as well as the specific interactions between active site residues and small-molecule inhibitors. Comparison of the two structures suggests that native glycosylation may be required for DPP IV oligomerization.
10. ••].
11. Hughes T.E., Mone M.D., Russell M.E., Weldon S.C., Villhauer E.B. NVP-DPP728 (1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)- pyrrolidine), a slow-binding inhibitor of dipeptidyl peptidase IV. Biochemistry. 38:1999;11597-11603.
12. Marguet D., Baggio L., Kobayashi T., Bernard A.M., Pierres M., Nielsen P.F., Ribel U., Watanabe T., Drucker D.J., Wagtmann N. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc. Natl. Acad Sci. USA. 97:2000;6874-6879 Characterization of a DPP IV-deficient mouse strain was critical in establishing DPP IV as a viable drug target for type 2 diabetes.
13. Watanabe Y., Kojima T., Fujimoto Y. Deficiency of membrane-bound dipeptidyl aminopeptidase IV in certain rat strain. Experientia. 43:1987;400-401.
14. Drucker D.J. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology. 122:2002;531-544.
15. Conarello S.L., Li Z., Ronan J., Roy R.S., Zhu L., Jiang G., Liu F., Woods J., Zycband E., Moller D.E.et al. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc. Natl. Acad Sci. USA. 100:2003;6825-6830 Further characterization of the DPP IV deficient mice generated by Marguet et al. suggests that DPP IV inhibitors may be useful in the treatment of obesity in addition to diabetes.
16. Nagakura T., Yasuda N., Yamazaki K., Ikuta H., Yoshikawa S., Asano O., Tanaka I. Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats. Biochem. Biophys. Res. Commun. 284:2001;501-506.
17. Yasuda N., Nagakura T., Yamazaki K., Inoue T., Tanaka I. Improvement of high fat-diet-induced insulin resistance in dipeptidyl peptidase IV-deficient Fischer rats. Life Sci. 71:2002;227-238.
18. Holst J.J. Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors. Adv. Exp. Med. Biol. 524:2003;263-279.
19. Drucker D.J. Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes. Expert. Opin. Investig. Drugs. 12:2003;87-100.
20. 1c, was shown in the first report of clinical utility of a DPP IV inhibitor in human diabetics.
21. •], details long-term effects of DPP IV inhibition in rodents. Taken together, the studies provide additional support for the notion that chronic inhibition of DPP IV will be a feasible method for the control of type 2 diabetes.
22. •].
23. •].
24. •].
25. Pospisilik J.A., Martin J., Doty T., Ehses J.A., Pamir N., Lynn F.C., Piteau S., Demuth H.U., McIntosh C.H., Pederson R.A. Dipeptidyl peptidase IV inhibitor treatment stimulates beta-cell survival and islet neogenesis in streptozotocin-induced diabetic rats. Diabetes. 52:2003;741-750 This study is significant as the results suggest that DPP IV inhibitors may be useful for type 1 (insulin dependent) diabetes.
26. Richard E., Alam S.M., Arredondo-Vega F.X., Patel D.D., Hershfield M.S. Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV. J. Biol. Chem. 277:2002;19720-19726.
27. Dinjens W.N., ten Kate J., Wijnen J.T., van der Linden E.P., Beek C.J., Lenders M.H., Khan P.M., Bosman F.T. Distribution of adenosine deaminase-complexing protein in murine tissues. J. Biol. Chem. 264:1989;19215-19220.
28. Kobayashi H., Hosono O., Mimori T., Kawasaki H., Dang N.H., Tanaka H., Morimoto C. Reduction of serum soluble CD26/dipeptidyl peptidase IV enzyme activity and its correlation with disease activity in systemic lupus erythematosus. J. Rheumatol. 29:2002;1858-1866.
29. Khin E.E., Kikkawa F., Ino K., Kajiyama H., Suzuki T., Shibata K., Tamakoshi K., Nagasaka T., Mizutani S. Dipeptidyl peptidase IV expression in endometrial endometrioid adenocarcinoma and its inverse correlation with tumor grade. Am. J. Obstet. Gynecol. 188:2003;670-676.
30. Sun S., Albright C.F., Fish B.H., George H.J., Selling B.H., Hollis G.F., Wynn R. Expression, purification, and kinetic characterization of full-length human fibroblast activation protein. Protein Expr. Purif. 24:2002;274-281.
31. Park J.E., Lenter M.C., Zimmermann R.N., Garin-Chesa P., Old L.J., Rettig W.J. Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts. J. Biol. Chem. 274:1999;36505-36512.
32. Chen W.T. DPPIV and seprase in cancer invasion and angiogenesis. Adv. Exp. Med. Biol. 524:2003;197-203.
33. Ghersi G., Dong H., Goldstein L.A., Yeh Y., Hakkinen L., Larjava H.S., Chen W.T. Regulation of fibroblast migration on collagenous matrix by a cell surface peptidase complex. J. Biol. Chem. 277:2002;29231-29241 This study showed that DPP IV and FAP are present in a complex. This complex could be relevant to overlap in the biological processes in which DPP IV and FAP are involved.
34. Cheng J.D., Dunbrack R.L. Jr., Valianou M., Rogatko A., Alpaugh R.K., Weiner L.M. Promotion of tumor growth by murine fibroblast activation protein, a serine protease, in an animal model. Cancer Res. 62:2002;4767-4772 Strong evidence is provided in this study for a role of FAP in tumor growth and, importantly, for inhibitors of FAP, including antibodies, in controlling tumor growth.
35. Hofheinz R.D., Al-Batran S.E., Hartmann F., Hartung G., Jager D., Renner C., Tanswell P., Kunz U., Amelsberg A., Kuthan H.et al. Stromal antigen targeting by a humanised monoclonal antibody: an early Phase II trial of sibrotuzumab in patients with metastatic colorectal cancer. Onkologie. 26:2003;44-48.
36. Niedermeyer J., Kriz M., Hilberg F., Garin-Chesa P., Bamberger U., Lenter M.C., Park J., Viertel B., Puschner H., Mauz M.et al. Targeted disruption of mouse fibroblast activation protein. Mol. Cell Biol. 20:2000;1089-1094.
37. Jones B, Adams S, Miller GT, Jesson MI, Watanabe T, Wallner BP: Hematopoietic stimulation by a dipeptidyl peptidase inhibitor reveals a novel regulatory mechanism and therapeutic treatment for blood cell deficiencies. Blood 2003, in press.
38. Abbott C.A., Yu D.M., Woollatt E., Sutherland G.R., McCaughan G.W., Gorrell M.D. Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. Eur. J. Biochem. 267: 2000;6140-6150 Two additional members of the DPP-IV-like family were cloned, and initial characterization of DPP 8 was provided.
39. Olsen C., Wagtmann N. Identification and characterization of human DPP9, a novel homologue of dipeptidyl peptidase IV. Gene. 299:2002;185-193.
40. Chiravuri M., Agarraberes F., Mathieu S.L., Lee H., Huber B.T. Vesicular localization and characterization of a novel post-proline-cleaving aminodipeptidase, quiescent cell proline dipeptidase. J. Immunol. 165:2000;5695-5702.
41. Underwood R., Chiravuri M., Lee H., Schmitz T., Kabcenell A.K., Yardley K., Huber B.T. Sequence, purification, and cloning of an intracellular serine protease, quiescent cell proline dipeptidase. J. Biol. Chem. 274:1999;34053-34058.
42. Chiravuri M., Schmitz T., Yardley K., Underwood R., Dayal Y., Huber B.T. A novel apoptotic pathway in quiescent lymphocytes identified by inhibition of a post-proline cleaving aminodipeptidase: a candidate target protease, quiescent cell proline dipeptidase. J. Immunol. 163:1999;3092-3099 The authors, having discovered that dipeptidyl peptidase inhibitors lead to apoptosis in quiescent lympohcytes, identify the enzyme that is likely to be responsible for that effect. As a result, DPP 7 emerged as a possibly important player in apoptosis.
43. Chiravuri M., Huber B.T. Aminodipeptidase inhibitor-induced cell death in quiescent lymphocytes: a review. Apoptosis. 5:2000;319-322.
44. Leiting B., Pryor K.D., Wu J.K., Marsilio F., Patel R.A., Craik C.S., Ellman J.A., Cummings R.T., Thornberry N.A. Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII. Biochem. J. 371:2003;525-532.
45. Senten K., Van der Veken P., Bal G., De Meester I., Lambeir A.M., Scharpe S., Bauvois B., Haemers A., Augustyns K. Development of potent and selective dipeptidyl peptidase II inhibitors. Bioorg. Med. Chem. Lett. 12:2002;2825-2828.
46. Chiravuri M., Lee H., Mathieu S.L., Huber B.T. Homodimerization via a leucine zipper motif is required for enzymatic activity of quiescent cell proline dipeptidase. J. Biol. Chem. 275:2000;26994-26999.
47. Shariat-Madar Z., Mahdi F., Schmaier A.H. Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator. J. Biol. Chem. 277:2002;17962-17969.
48. Goossens F., De Meester I., Vanhoof G., Scharpe S. Distribution of prolyl oligopeptidase in human peripheral tissues and body fluids. Eur. J. Clin. Chem. Clin. Biochem. 34:1996;17-22.
49. Fulop V., Bocskei Z., Polgar L. Prolyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis. Cell. 94:1998;161-170.
50. Cunningham D.F., O'Connor B. Proline specific peptidases. Biochim. Biophys. Acta. 1343:1997;160-186.
51. Yoshimoto T., Kado K., Matsubara F., Koriyama N., Kaneto H., Tsura D. Specific inhibitors for prolyl endopeptidase and their anti-amnesic effect. J. Pharmacobiodyn. 10:1987;730-735.
52. Portevin B., Benoist A., Remond G., Herve Y., Vincent M., Lepagnol J., De Nanteuil G. New prolyl endopeptidase inhibitors: in vitro and in vivo activities of azabicyclo[2.2.2]octane, azabicyclo[2.2.1]heptane, and perhydroindole derivatives. J. Med. Chem. 39:1996;2379-2391.
53. Katsube N., Sunaga K., Aishita H., Chuang D.M., Ishitani R. ONO-1603, a potential antidementia drug, delays age-induced apoptosis and suppresses overexpression of glyceraldehyde-3-phosphate dehydrogenase in cultured central nervous system neurons. J. Pharmacol. Exp. Ther. 288:1999;6-13.
54. Schulz I., Gerhartz B., Neubauer A., Holloschi A., Heiser U., Hafner M., Demuth H.U. Modulation of inositol 1,4,5-triphosphate concentration by prolyl endopeptidase inhibition. Eur. J. Biochem. 269:2002;5813-5820.
55. Bellemere G., Morain P., Vaudry H., Jegou S. Effect of S 17092, a novel prolyl endopeptidase inhibitor, on substance P and alpha-melanocyte-stimulating hormone breakdown in the rat brain. J. Neurochem. 84:2003;919-929.
56. Williams R.S., Cheng L., Mudge A.W., Harwood A.J. A common mechanism of action for three mood-stabilizing drugs. Nature. 417:2002;292-295 An intriguing report that POP may have a central role in the biological activity of commonly used therapeutics for the treatment of neurological disorders.
57. Richards P., Lees J. Functional proteomics using microchannel plate detectors. Proteomics. 2:2002;256-261.
58. Duysen E.G., Li B., Xie W., Schopfer L.M., Anderson R.S., Broomfield C.A., Lockridge O. Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to VX lethality. J. Pharmacol. Exp. Ther. 299:2001;528-535.
59. Xie W., Stribley J.A., Chatonnet A., Wilder P.J., Rizzino A., McComb R.D., Taylor P., Hinrichs S.H., Lockridge O. Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J. Pharmacol. Exp. Ther. 293:2000;896-902.
60. Richards P.G., Johnson M.K., Ray D.E. Identification of acylpeptide hydrolase as a sensitive site for reaction with organophosphorus compounds and a potential target for cognitive enhancing drugs. Mol. Pharmacol. 58:2000;577-583.
61. Qi S.Y., Riviere P.J., Trojnar J., Junien J.L., Akinsanya K.O. Cloning and characterization of dipeptidyl peptidase 10 (DPP10), a new member of an emerging subgroup of serine proteases. Biochem. J. 373:2003;179-189.
62. Hough R.B., Lengeling A., Bedian V., Lo C., Bucan M. Rump white inversion in the mouse disrupts dipeptidyl aminopeptidase-like protein 6 and causes dysregulation of Kit expression. Proc. Natl. Acad Sci. USA. 95:1998;13800-13805.
63. Nadal M.S., Ozaita A., Amarillo Y., de Miera E.V., Ma Y., Mo W., Goldberg E.M., Misumi Y., Ikehara Y., Neubert T.A.et al. The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels. Neuron. 37:2003;449-461 The observation that a proteolytically inactive homolog of DPP IV is an essential component in ion channels is suggestive that other DPP-IV-like proteins could be involved in similar, yet to be determined, protein assemblages.
64. Duke-Cohan J.S., Gu J., McLaughlin D.F., Xu Y., Freeman G.J., Schlossman S.F. Attractin (DPPT-L), a member of the CUB family of cell adhesion and guidance proteins, is secreted by activated human T lymphocytes and modulates immune cell interactions. Proc. Natl. Acad Sci. USA. 95:1998;11336-11341.
65. Friedrich D., Kuhn-Wache K., Hoffmann T., Demuth H.U. Isolation and characterization of attractin-2. Adv. Exp. Med. Biol. 524:2003;109-113.
66. Durinx C., Lambeir A.M., Bosmans E., Falmagne J.B., Berghmans R., Haemers A., Scharpe S., De Meester I. Molecular characterization of dipeptidyl peptidase activity in serum: soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides. Eur. J. Biochem. 267:2000;5608-5613 Purification and quantification of DPP IV from human serum indicates that at approximately 5 nM, DPP IV is the only significant source of X-Pro amino dipeptidase activity from this source.
67. Malik R., Mares V., Kleibl Z., Pohlreich P., Vlasicova K., Sedo A. Expression of attractin and its differential enzyme activity in glioma cells. Biochem. Biophys. Res. Commun. 284:2001;289-294.
68. Gunn T.M., Inui T., Kitada K., Ito S., Wakamatsu K., He L., Bouley D.M., Serikawa T., Barsh G.S. Molecular and phenotypic analysis of Attractin mutant mice. Genetics. 158:2001;1683-1695.
69. Pangalos M.N., Neefs J.M., Somers M., Verhasselt P., Bekkers M., van der Helm L., Fraiponts E., Ashton D., Gordon R.D. Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity. J. Biol. Chem. 274:1999;8470-8483.
70. Barinka C., Rinnova M., Sacha P., Rojas C., Majer P., Slusher B.S., Konvalinka J. Substrate specificity, inhibition and enzymological analysis of recombinant human glutamate carboxypeptidase II. J. Neurochem. 80:2002;477-487.