B1–Proteases As Molecular Targets of Drug Development
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(12) United States Patent (10) Patent No.: US 6,395,889 B1 Robison (45) Date of Patent: May 28, 2002
USOO6395889B1 (12) United States Patent (10) Patent No.: US 6,395,889 B1 Robison (45) Date of Patent: May 28, 2002 (54) NUCLEIC ACID MOLECULES ENCODING WO WO-98/56804 A1 * 12/1998 ........... CO7H/21/02 HUMAN PROTEASE HOMOLOGS WO WO-99/0785.0 A1 * 2/1999 ... C12N/15/12 WO WO-99/37660 A1 * 7/1999 ........... CO7H/21/04 (75) Inventor: fish E. Robison, Wilmington, MA OTHER PUBLICATIONS Vazquez, F., et al., 1999, “METH-1, a human ortholog of (73) Assignee: Millennium Pharmaceuticals, Inc., ADAMTS-1, and METH-2 are members of a new family of Cambridge, MA (US) proteins with angio-inhibitory activity', The Journal of c: - 0 Biological Chemistry, vol. 274, No. 33, pp. 23349–23357.* (*) Notice: Subject to any disclaimer, the term of this Descriptors of Protease Classes in Prosite and Pfam Data patent is extended or adjusted under 35 bases. U.S.C. 154(b) by 0 days. * cited by examiner (21) Appl. No.: 09/392, 184 Primary Examiner Ponnathapu Achutamurthy (22) Filed: Sep. 9, 1999 ASSistant Examiner William W. Moore (51) Int. Cl." C12N 15/57; C12N 15/12; (74) Attorney, Agent, or Firm-Alston & Bird LLP C12N 9/64; C12N 15/79 (57) ABSTRACT (52) U.S. Cl. .................... 536/23.2; 536/23.5; 435/69.1; 435/252.3; 435/320.1 The invention relates to polynucleotides encoding newly (58) Field of Search ............................... 536,232,235. identified protease homologs. The invention also relates to 435/6, 226, 69.1, 252.3 the proteases. The invention further relates to methods using s s s/ - - -us the protease polypeptides and polynucleotides as a target for (56) References Cited diagnosis and treatment in protease-mediated disorders. -
Serine Proteases with Altered Sensitivity to Activity-Modulating
(19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants. -
Subtilase Variants
(19) & (11) EP 2 333 055 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 15.06.2011 Bulletin 2011/24 C12N 9/54 (2006.01) C11D 3/386 (2006.01) C12N 1/15 (2006.01) C12N 1/19 (2006.01) (2006.01) (21) Application number: 10180093.6 C12N 1/21 (22) Date of filing: 12.10.2001 (84) Designated Contracting States: (72) Inventors: AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU • Nørregaard-Madsen, Mads MC NL PT SE TR DK-3560, Birkerød (DK) • Larsen, Line, Bloch (30) Priority: 13.10.2000 DK 200001528 DK-2880, Bagsværd (DK) • Hansen, Peter Kamp (62) Document number(s) of the earlier application(s) in DK-4320, Lejre (DK) accordance with Art. 76 EPC: 01978206.9 / 1 326 966 Remarks: This application was filed on 27-09-2010 as a (71) Applicant: Novozymes A/S divisional application to the application mentioned 2880 Bagsvaerd (DK) under INID code 62. (54) Subtilase variants (57) Novel subtilase variants having a reduced ten- dry detergent compositions and dishwash composition, dency towards inhibition by substances present in eggs, including automatic dishwash compositions. Also, isolat- such as trypsin inhibitor type IV- 0. In particular, variants ed DNA sequences encoding the variants, expression comprising at least one additional amino acid residue vectors, host cells, and methods for producing and using between positions 42-43, 51-56, 155-161, 187-190, the variants of the invention. Further, cleaning and de- 216-217, 217-218 or 218-219 (in BASBPN numbering). tergent compositions comprising the variants are dis- These subtilase variants are useful exhibiting excellent closed. -
Role of Amylase in Ovarian Cancer Mai Mohamed University of South Florida, [email protected]
University of South Florida Scholar Commons Graduate Theses and Dissertations Graduate School July 2017 Role of Amylase in Ovarian Cancer Mai Mohamed University of South Florida, [email protected] Follow this and additional works at: http://scholarcommons.usf.edu/etd Part of the Pathology Commons Scholar Commons Citation Mohamed, Mai, "Role of Amylase in Ovarian Cancer" (2017). Graduate Theses and Dissertations. http://scholarcommons.usf.edu/etd/6907 This Dissertation is brought to you for free and open access by the Graduate School at Scholar Commons. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. Role of Amylase in Ovarian Cancer by Mai Mohamed A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Pathology and Cell Biology Morsani College of Medicine University of South Florida Major Professor: Patricia Kruk, Ph.D. Paula C. Bickford, Ph.D. Meera Nanjundan, Ph.D. Marzenna Wiranowska, Ph.D. Lauri Wright, Ph.D. Date of Approval: June 29, 2017 Keywords: ovarian cancer, amylase, computational analyses, glycocalyx, cellular invasion Copyright © 2017, Mai Mohamed Dedication This dissertation is dedicated to my parents, Ahmed and Fatma, who have always stressed the importance of education, and, throughout my education, have been my strongest source of encouragement and support. They always believed in me and I am eternally grateful to them. I would also like to thank my brothers, Mohamed and Hussien, and my sister, Mariam. I would also like to thank my husband, Ahmed. -
Fibronectin-Binding Protein B (Fnbpb)
ARTICLE cro Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones Received for publication, September 5, 2018, and in revised form, December 17, 2018 Published, Papers in Press, January 8, 2019, DOI 10.1074/jbc.RA118.005707 X Giampiero Pietrocola‡1, Giulia Nobile‡, Mariangela J. Alfeo‡, Timothy J. Foster§, Joan A. Geoghegan¶, Vincenzo De Filippisʈ, and X Pietro Speziale‡**2 From the ‡Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, 27100 Pavia, Italy, the §Microbiology Department, Trinity College Dublin, Dublin 2, Ireland, the ¶Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Dublin 2, Ireland, the ʈLaboratory of Protein Chemistry and Molecular Hematology, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 36131 Padova, Italy, and the **Department of Industrial and Information Engineering, University of Pavia, 27100 Pavia, Italy Edited by Roger J. Colbran Staphylococcus aureus is a Gram-positive bacterium that can tizing pneumoniae (1, 2). Strains that are resistant to multiple Downloaded from cause both superficial and deep-seated infections. Histones antibiotics are a major problem in healthcare settings in devel- released by neutrophils kill bacteria by binding to the bacterial oped countries (3). These are referred to as hospital-associated cell surface and causing membrane damage. We postulated that methicillin-resistant S. aureus (MRSA)3 and occur in individu- cell wall–anchored proteins protect S. aureus from the bacteri- als with pre-disposing risk factors, such as surgical wounds and cidal effects of histones by binding to and sequestering histones indwelling medical devices (4, 5). -
Gpi-Anchored Proteins in Reconstituted Lipid Bilayers
GPI-ANCHORED PROTEINS IN RECONSTITUTED LIPID BILAYERS: STRUCTURE, FUNCTION, AND CLEAVAGE BY PI-SPECFIC PHOSPHOLIPASE C A Thesis Presented to The Faculty of Graduate Studies of The University of Guelph by MARTY T. LEHTO In partial fulfilrnent of requirements for the degree of Doctor of Philosophy August 2001 O Marty T. Lehto, 2001 National Library Bibliothèque nationale 1+1 of Canada du Canada Acquisitions and Acquisitions et Bibliographie Services services bibliographiques 395 Wellington Street 395. rue Wellington Ottawa ON Kt A ON4 Ottawa ON K1A ON4 Canada Canada Your file Votre r4f8me Our file Notre réfdrence The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant a la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sell reproduire, prêter, distribuer ou copies of this thesis in microfonq vendre des copies de cette thèse sous paper or electronic formats. la fome de microfiche/film, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels May be printed or othenuise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. GPI-ANCHORED PROTEINS IN RECONSTITUTED LEPID BILAYERS: STRUCTURE, FUNCTION AND CLEAVAGE BY PI-SPECFIC PHOSPHOLPASE C Marty T. Lehto Advisor: University of Guelph, 200 1 Professor F.J. Sharom Many eukaryotic proteins are anchored to the ce11 surface by a glycosylphosphatidylinositol (GPI) moiety. -
Characterisation of the Major Extracellular Proteases of Stenotrophomonas Maltophilia and Their Effects on Pulmonary Antiproteases
pathogens Article Characterisation of the Major Extracellular Proteases of Stenotrophomonas maltophilia and Their Effects on Pulmonary Antiproteases Kevin Molloy 1, Stephen G. Smith 2, Gerard Cagney 3, Eugene T. Dillon 3, Catherine M. Greene 4,* and Noel G. McElvaney 1 1 Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, D02 YN77 Dublin, Ireland 2 Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland 3 School of Biomolecular and Biomedical Science, University College Dublin, D04 V1W8 Dublin, Ireland 4 Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Beaumont Hospital, D02 YN77 Dublin, Ireland * Correspondence: [email protected] Received: 31 May 2019; Accepted: 22 June 2019; Published: 28 June 2019 Abstract: Stenotrophomonas maltophilia is an emerging global opportunistic pathogen that has been appearing with increasing prevalence in cystic fibrosis (CF). A secreted protease from S. maltophilia has been reported as its chief potential virulence factor. Here, using the reference clinical strain S. maltophilia K279a, the major secreted proteases were identified. Protein biochemistry and mass spectrometry were carried out on K279a culture supernatant. The effect of K279a culture supernatant on cleavage and anti-neutrophil elastase activity of the three majors pulmonary antiproteases was quantified. A deletion mutant of S. maltophilia lacking expression of a protease was constructed. The serine proteases StmPR1, StmPR2 and StmPR3, in addition to chitinase A and an outer membrane esterase were identified in culture supernatants. Protease activity was incompletely abrogated in a K279a-DStmPR1: Erm mutant. Wild type K279a culture supernatant degraded alpha-1 antitrypsin (AAT), secretory leucoprotease inhibitor (SLPI) and elafin, important components of the lung’s innate immune defences. -
Final Program
In Memoriam: Final Program XXV Congress of the International Society on Thrombosis and Haemostasis and 61st Annual SSC Meeting June 20 – 25, 2015 Toronto, Canada www.isth2015.org 1 Final Program Table of Contents 3 Venue and Contacts 5 Invitation and Welcome Message 12 ISTH 2015 Committees 24 Congress Support 25 Sponsors and Exhibitors 27 ISTH Awards 32 ISTH Society Information 37 Program Overview 41 Program Day by Day 55 SSC and Educational Program 83 Master Classes and Career Mentorship Sessions 87 Nurses Forum 93 Scientific Program, Monday, June 22 94 Oral Communications 1 102 Plenary Lecture 103 State of the Art Lectures 105 Oral Communications 2 112 Abstract Symposia 120 Poster Session 189 Scientific Program, Tuesday, June 23 190 Oral Communications 3 198 Plenary Lecture 198 State of the Art Lectures 200 Oral Communications 4 208 Plenary Lecture 209 Abstract Symposia 216 Poster Session 285 Scientific Program, Wednesday, June 24 286 Oral Communications 5 294 Plenary Lecture 294 State of the Art Lectures 296 Oral Communications 6 304 Abstract Symposia 311 Poster Session 381 Scientific Program, Thursday, June 25 382 Oral Communications 7 390 Plenary Lecture 390 Abstract Symposia 397 Highlights of ISTH 399 Exhibition Floor Plan 402 Exhibitor List 405 Congress Information 406 Venue Plan 407 Congress Information 417 Social Program 418 Toronto & Canada Information 421 Transportation in Toronto 423 Future ISTH Meetings and Congresses 2 427 Authors Index 1 Thank You to Everyone Who Supported the Venue and Contacts 2014 World Thrombosis Day -
The Utilization of Alpha-1 Anti-Trypsin (A1AT) in Infectious Disease Monitoring and Treatment Irene L
JMID/ 2019; 9 (1):51-58 Journal of Microbiology and Infectious Diseases doi: 10.5799/jmid.537178 REVIEW ARTICLE The Utilization of Alpha-1 Anti-trypsin (A1AT) in Infectious Disease Monitoring and Treatment Irene L. Indalao, Agustiningsih Agustiningsih, Eka Pratiwi, Kartika Dewi Puspa, Hartanti Dian Ikawati, Ririn Ramadhany Center for Research and Development of Biomedical and Basic Technology of Health, National Institute of Health Research and Development, Ministry of Health Republic of Indonesia ABSTRACT Alpha one anti-trypsin (A1AT) is a major serine protease inhibitor found circulating in human blood. A1AT related studies mainly focus on A1AT potential biomarker as well as therapeutic target in non-infectious diseases. Their findings indicate A1AT beneficial features may also be applied for monitoring and treating infectious disease. However, only a few studies have reviewed A1AT’s useful properties as a biomarker and therapeutic agent for infectious diseases. This narrative review aims to summarize growing evidences that support the idea of utilizing A1AT as a tool for monitoring and therapy for infectious diseases. A1AT showed potential as a biomarker for a wide spectrum of infectious disease, from virus, bacteria, to parasite. Its level and functionality were proposed to predict risk for disease susceptibility or progression and to indicate response therapy. As promising therapeutic agent in various infectious diseases, the administration of A1AT has shown antimicrobial activity, immunomodulatory and anti-apoptotic effect, in addition to more familiar function, suppressing excessive proteolysis. The broad utilization of A1AT, both as biomarker and therapeutic agent, in studies on infectious diseases seems promising. However, there are issues need to be investigated further before establishing its feasibility as a monitoring and therapy tool against infection diseases. -
Center for Drug Evaluation and Research Application
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 22-512 PHARMACOLOGY REVIEW(S) Tertiary Pharmacology Review By: Paul C. Brown, Ph.D., ODE Associate Director for Pharmacology and Toxicology OND IO NDA: 22-307 Submission date: 4/19/2010 Drug: Pradaxa™ (Dabigatran etexilate mesylate) Sponsor: Boehringer Ingelheim Pharma GmbH & Co. KG Indication: Prevention of stroke and systemic embolism in patients with atrial fibrillation Reviewing Division: Division of Cardiovascular and Renal Products Comments: The pharm/tox reviewer and supervisor found the nonclinical information submitted for dabigatran to be sufficient to support the proposed use. The reviewer proposes pregnancy category C for the labeling. Dabigatran induced some reproductive toxicity in rats manifest as a decreased number of implantations, decreased number of viable fetuses, increase in the resorption rate, increase in post-implantation loss, and an increase in the number of dead offspring when given at doses of 70 mg/kg (about 2.6 to 3 times the MRHD of 300 mg/day on a mg/m2 basis). Dabigatran also induced some fetal structural variations but did not induce fetal malformations in rats or rabbits. Dabigatran was evaluated for carcinogenicity in 2-year rat and mouse studies. The Executive Carcinogenicity Assessment Committee concluded that these studies were adequate and there were no drug-related tumors in either study. Conclusions: I concur with the Division pharm/tox conclusion that the nonclinical data support approval of this NDA. No additional nonclinical studies are recommended at this time. The proposed Established Pharmacologic Class for dabigatran is "direct thrombin inhibitor". This is appropriate because it is consistent with other moieties of this class. -
Shedding and Uptake of Gangliosides and Glycosylphosphatidylinositol-Anchored Proteins ⁎ Gordan Lauc A,B, , Marija Heffer-Lauc C
Biochimica et Biophysica Acta 1760 (2006) 584–602 http://www.elsevier.com/locate/bba Review Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins ⁎ Gordan Lauc a,b, , Marija Heffer-Lauc c a Department of Chemistry and Biochemistry, University of Osijek School of Medicine, J. Huttlera 4, 31000 Osijek, Croatia b Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia c Department of Biology, University of Osijek School of Medicine, J. Huttlera 4, 31000 Osijek, Croatia Received 30 September 2005; received in revised form 22 November 2005; accepted 23 November 2005 Available online 20 December 2005 Abstract Gangliosides and glycosylphosphatidylinositol (GPI)-anchored proteins have very different biosynthetic origin, but they have one thing in common: they are both comprised of a relatively large hydrophilic moiety tethered to a membrane by a relatively small lipid tail. Both gangliosides and GPI-anchored proteins can be actively shed from the membrane of one cell and taken up by other cells by insertion of their lipid anchors into the cell membrane. The process of shedding and uptake of gangliosides and GPI-anchored proteins has been independently discovered in several disciplines during the last few decades, but these discoveries were largely ignored by people working in other areas of science. By bringing together results from these, sometimes very distant disciplines, in this review, we give an overview of current knowledge about shedding and uptake of gangliosides and GPI-anchored proteins. Tumor cells and some pathogens apparently misuse this process for their own advantage, but its real physiological functions remain to be discovered. -
Handbook of Proteolytic Enzymes Second Edition Volume 1 Aspartic and Metallo Peptidases
Handbook of Proteolytic Enzymes Second Edition Volume 1 Aspartic and Metallo Peptidases Alan J. Barrett Neil D. Rawlings J. Fred Woessner Editor biographies xxi Contributors xxiii Preface xxxi Introduction ' Abbreviations xxxvii ASPARTIC PEPTIDASES Introduction 1 Aspartic peptidases and their clans 3 2 Catalytic pathway of aspartic peptidases 12 Clan AA Family Al 3 Pepsin A 19 4 Pepsin B 28 5 Chymosin 29 6 Cathepsin E 33 7 Gastricsin 38 8 Cathepsin D 43 9 Napsin A 52 10 Renin 54 11 Mouse submandibular renin 62 12 Memapsin 1 64 13 Memapsin 2 66 14 Plasmepsins 70 15 Plasmepsin II 73 16 Tick heme-binding aspartic proteinase 76 17 Phytepsin 77 18 Nepenthesin 85 19 Saccharopepsin 87 20 Neurosporapepsin 90 21 Acrocylindropepsin 9 1 22 Aspergillopepsin I 92 23 Penicillopepsin 99 24 Endothiapepsin 104 25 Rhizopuspepsin 108 26 Mucorpepsin 11 1 27 Polyporopepsin 113 28 Candidapepsin 115 29 Candiparapsin 120 30 Canditropsin 123 31 Syncephapepsin 125 32 Barrierpepsin 126 33 Yapsin 1 128 34 Yapsin 2 132 35 Yapsin A 133 36 Pregnancy-associated glycoproteins 135 37 Pepsin F 137 38 Rhodotorulapepsin 139 39 Cladosporopepsin 140 40 Pycnoporopepsin 141 Family A2 and others 41 Human immunodeficiency virus 1 retropepsin 144 42 Human immunodeficiency virus 2 retropepsin 154 43 Simian immunodeficiency virus retropepsin 158 44 Equine infectious anemia virus retropepsin 160 45 Rous sarcoma virus retropepsin and avian myeloblastosis virus retropepsin 163 46 Human T-cell leukemia virus type I (HTLV-I) retropepsin 166 47 Bovine leukemia virus retropepsin 169 48