DOCSLIB.ORG

Efficacy of Polymeric Encapsulated C5a Peptidase–Based Group B

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Efficacy of Polymeric Encapsulated C5a Peptidase–Based Group B SMFM Papers www.AJOG.org Efficacy of polymeric encapsulated C5a peptidase–based group B streptococcus vaccines in a murine model Donna A. Santillan, PhD; Karishma K. Rai, MD; Mark K. Santillan, MD; Yogita Krishnamachari, PhD; Aliasger K. Salem, PhD; Stephen K. Hunter, MD, PhD OBJECTIVE: The purpose was to examine in mice the efficacy of vari- RESULTS: Thirty microgram doses of the 75:25 and 50:50 PLGA for- ous polymeric-encapsulated C5a peptidase vaccine formulations in mulations generate the highest and most sustained C5a peptidase– eliciting a long-term immune response and preventing group B strepto- specific immune responses. Mice that received encapsulated C5a pep- coccus (GBS) infection. tidase were significantly protected from vaginal colonization compared STUDY DESIGN: C5a peptidase was encapsulated in semiperme- with mice that received empty microspheres. able microspheres of poly(lactide-coglycolide) (PLGA). Female ICR CONCLUSION: Encapsulated C5a peptidase elicited significant immune mice were immunized with 0, 10, or 30 ␮g of encapsulated C5a responses and protection against a GBS challenge. C5a peptidase mi- peptidase within 2 different formulations of PLGA polymers. Booster crosphere encapsulation has potential as a GBS vaccine. doses were given at weeks 4 and 8. Antibody responses were mea- sured by enzyme-linked immunosorbent assay at weeks 4, 8, 11, Key words: antigen encapsulation, C5a peptidase, group B and 40. Vaginal challenges with GBS types 1a, III, and V were per- streptococcus, microparticle, microsphere, mouse, poly(lactide- formed at week 12. coglycolide), vaccine Cite this article as: Santillan DA, Rai KK, Santillan MK, et al. Efficacy of polymeric encapsulated C5a peptidase–based group B streptococcus vaccines in a murine model. Am J Obstet Gynecol 2011;205:249.e1-8. roup B streptococci are Gram-posi- colonize the intestinal and urogenital tract adults and pregnant women in the top Gtive diplococci that produce polysac- of healthy adults without causing any com- tier for vaccine development.3 They sug- charide capsules.1 There are 10 different plications. However, GBS infections can gested the vaccine would have the great- Group B Streptococcus (GBS) serotypes, cause serious problems in pregnancy. est effect if given as part of routine pre- based on the antigenic variation of the cap- In 1985, the Institute of Medicine natal care for all women in their first sular polysaccharides. These serotypes are from the National Academies of Sciences pregnancy. Maternal complications of Ia, Ib, and II through IX. A recent interna- indicated that a vaccine for GBS should GBS infections in pregnancy include uri- tional study most commonly isolated sero- be a high priority. In a 1999 report, they nary tract infections, chorioamnionitis, 2 types III and V from patients. GBS can again listed a GBS vaccine for high-risk postpartum wound infection, pyelone- phritis, postpartum endometritis, and sepsis. For the neonate, preterm prema- From the Divisions of Reproductive Health Research (Drs D. A. Santillan, M. K. Santillan, ture rupture of membranes (PPROM), and Hunter) and Maternal-Fetal Medicine (Drs Rai, M. K. Santillan, and Hunter), neonatal pneumonia, sepsis, meningitis, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, and the or death can occur as a consequence of Division of Pharmaceutics, University of Iowa College of Pharmacy (Drs Krishnamachari and 4-8 Salem), Iowa City, IA. GBS. Because GBS infection continues to be Presented, in part, at the 31st Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 7-12, 2011. a serious concern during pregnancy, the Received March 10, 2011; revised April 26, 2011; accepted June 7, 2011. updated guidelines from the Centers for Reprints: Stephen K. Hunter, MD, PhD, University of Iowa Hospitals and Clinics, Department of Disease Control and Prevention con- Obstetrics and Gynecology, 200 Hawkins Dr., Iowa City, IA 52242. [email protected]. tinue to recommend universal culture- This work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health based screening of all pregnant women at and Human Development, National Institutes of Health (NIH), Grant no. 1R03HD056006 (S.K.H.); 35-37 weeks’ gestation.9,10 Currently, if a Children’s Miracle Network and the University of Iowa Children’s Hospital (D.A.S.); NIH pregnant woman screens positive for Interdisciplinary Immunology Postdoctoral Training Program, Grant no. T32 AI 007260 (D.A.S.); NIH Interdisciplinary Training Program in Pain Research, Grant no. T32 NS045549 (K.K.R.); NIH GBS, she will receive intravenous antibi- University of Iowa Institute for Clinical and Translational Science Grant no. KL2 RR024980-2 otics during labor to prevent early-onset (M.K.S.); Department of Obstetrics and Gynecology, American Cancer Society Grant no. GBS disease in the child, which can in- RSG-09-015-01-CDD (A.K.S.); National Cancer Institute/NIH Grant nos. 1R21CA13345-01/ clude sepsis and death.9 Recent studies 1R21CA128414-01A2/UI, Mayo Clinic Lymphoma SPORE (A.K.S.); Pharmaceutical Research demonstrate that up to 24% of all preg- and Manufacturers of America (PhRMA) Foundation (A.K.S.); and support from a Guillory Fellowship (Y.K.). nant women receive antibiotic prophy- 0002-9378/$36.00 • © 2011 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2011.06.024 laxis for GBS. Between 50% and 75% of neonates exposed through the birth ca- SEPTEMBER 2011 American Journal of Obstetrics & Gynecology 249.e1 SMFM Papers www.AJOG.org nal of GBS-infected mothers will be highly conserved multifunctional surface and 50:50) would affect these immune colonized. protein that is expressed on the surface of responses and the ability of vaccinated Many shortcomings exist in the cur- all serotypes of both group A streptococcus mice to prevent GBS colonization and to rent therapy of antibiotic prophylaxis. (GAS) and group B streptococcus tes- pass GBS protection to pups of vacci- These shortcomings are especially evi- ted.17-20 C5a peptidase (ScpB) expressed nated dams. dent in cases in which a woman has a lack by GBS is 98% identical in sequence to that of prenatal care, delivers before being expressed by GAS.21,22 Structurally, C5a screened, delivers before the culture re- peptidase contains 5 domains including a MATERIALS AND METHODS sults return, has a rapid labor and does subtisilin-like protease domain, a pro- C5a peptidase encapsulation not finish receiving all of the antibiotic tease-associated domain, and 3 fibronectin C5a peptidase, guanosine monophosphate dose(s), or is allergic to antibiotics. In type III domains.23 The enzymatic activity prepared and greater than 98-99% pure, addition, the development of antibiotic of the peptidase is highly specific for C5a, was generously provided by Pfizer (Gro- resistance is an increasing problem. cleaving the chemotaxin at its polymor- ton, CT). The C5a peptidase was microen- Penicillin-tolerant strains of GBS have phonuclear leukocyte binding site.24 capsulated in PLGA microspheres. PLGA been identified, and resistance to other Recent evidence also suggests that C5a (50:50, inherent viscosity, 0.4 dL/g) and antibiotics has been documented.8,11 A peptidase may bind fibronectin to pro- PLGA (75:25, inherent viscosity, 0.51 recent study found 91% of strains iso- mote cellular invasion.25,26 Cheng et al27 dL/g) were purchased from Lactel Absorb- lated were resistant to erythromycin.12 demonstrated that ScpB increased the able Polymers (Cupertino, CA). Polyvinyl The consequences of a GBS infection in immunogenicity of a GBS type III poly- alcohol (PVA; 87-89% hydrolyzed, molec- pregnancy require that treatment be saccharide vaccine in mice when the 2 ular weight 30-67,000 Da) was purchased given. However, this large-scale use of were coupled. In addition, the investiga- from Sigma-Aldrich (St Louis, MO). antibiotics is contributing to the devel- tors found that ScpB was also found to Encapsulation was done using a water- opment of antibiotic resistance. Without induce the production of GBS serotype- in-oil-in-water (w/o/w) double-emulsion prevention strategies, such as vaccina- independent antibodies.27 technique as described previously.16,32,33 tion, our first-line antibiotic therapies We have previously shown that encap- Briefly, the internal aqueous phase con- are going to become useless against GBS. sulating C5a peptidase within micro- sisted of 3.6 mg peptidase equivalent to 6.6 Most importantly, this traditional ap- spheres composed of a copolymer of mg lyophilized powder C5a peptidase sol- proach does not prevent preterm deliv- lactic and glycolic acids, poly(lactide-co- ubilized in 500 ␮L of 1% (weight/volume) ery or PPROM or protect against late- glycolide) (PLGA), was able to induce aqueous solution of PVA as a surfactant. onset disease caused by GBS infection.13 systemic and mucosal immune response This was emulsified into an oil phase con- A GBS vaccine could overcome these in mice. Furthermore, this vaccine pro- taining 200 mg of PLGA 50:50 or PLGA pitfalls. vided protection in mice against GBS se- 75:25 dissolved in 5 mL dichloromethane Development of a vaccine for GBS has rotype III in vaginal and pup challenge (DCM) using a microtip probe sonicator. been hindered by several factors. First, studies.28 The PLGA polymer–based mi- This primary water/oil emulsion was then there are 10 serotypes of GBS that are based crospheres are able to act as an adjuvant poured into 50 mL of external aqueous on antigenic variation of the capsular poly- to the vaccine and are safe for use in hu- phase containing 1% (weight/volume) saccharides. Purified capsular polysaccha- mans and has been used for many years PVA as a surfactant and rapidly homoge- rides, without adjuvants, have elicited in resorbable sutures, bone plates, and nized using a high-speed homogenizer at weak immune responses in vaccines, and a commercial depot drug delivery formu- 9500 rpm for 30 seconds to form the sec- multivalent vaccine would be necessary to lations.29 The antigen release profile by ondary w/o/w emulsion.
Load more

Recommended publications
  • The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections
    toxins Review The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections Patience Shumba 1, Srikanth Mairpady Shambat 2 and Nikolai Siemens 1,* 1 Center for Functional Genomics of Microbes, Department of Molecular Genetics and Infection Biology, University of Greifswald, D-17489 Greifswald, Germany; [email protected] 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland; [email protected] * Correspondence: [email protected]; Tel.: +49-3834-420-5711 Received: 20 May 2019; Accepted: 10 June 2019; Published: 11 June 2019 Abstract: Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies. Keywords: Streptococcus pyogenes; group A streptococcus; Staphylococcus aureus; skin infections; necrotizing soft tissue infections; pore-forming toxins; superantigens; immunomodulatory proteases; immune responses Key Contribution: Group A streptococcal and Staphylococcus aureus toxins manipulate host physiological and immunological responses to promote disease severity and progression. 1. Introduction Necrotizing soft tissue infections (NSTIs) are rare and represent a more severe rapidly progressing form of soft tissue infections that account for significant morbidity and mortality [1].
    [Show full text]
  • Molecular Markers of Serine Protease Evolution
    The EMBO Journal Vol. 20 No. 12 pp. 3036±3045, 2001 Molecular markers of serine protease evolution Maxwell M.Krem and Enrico Di Cera1 ment and specialization of the catalytic architecture should correspond to signi®cant evolutionary transitions in the Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, history of protease clans. Evolutionary markers encoun- MO 63110-1093, USA tered in the sequences contributing to the catalytic apparatus would thus give an account of the history of 1Corresponding author e-mail: [email protected] an enzyme family or clan and provide for comparative analysis with other families and clans. Therefore, the use The evolutionary history of serine proteases can be of sequence markers associated with active site structure accounted for by highly conserved amino acids that generates a model for protease evolution with broad form crucial structural and chemical elements of applicability and potential for extension to other classes of the catalytic apparatus. These residues display non- enzymes. random dichotomies in either amino acid choice or The ®rst report of a sequence marker associated with serine codon usage and serve as discrete markers for active site chemistry was the observation that both AGY tracking changes in the active site environment and and TCN codons were used to encode active site serines in supporting structures. These markers categorize a variety of enzyme families (Brenner, 1988). Since serine proteases of the chymotrypsin-like, subtilisin- AGY®TCN interconversion is an uncommon event, it like and a/b-hydrolase fold clans according to phylo- was reasoned that enzymes within the same family genetic lineages, and indicate the relative ages and utilizing different active site codons belonged to different order of appearance of those lineages.
    [Show full text]
  • 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.
    [Show full text]
  • International Union of Basic and Clinical Pharmacology. LXXXVII
    Supplemental Material can be found at: /content/suppl/2014/09/18/65.1.500.DC1.html 1521-0081/65/1/500–543$25.00 http://dx.doi.org/10.1124/pr.111.005223 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:500–543, January 2013 Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors Andreas Klos, Elisabeth Wende, Kathryn J. Wareham, and Peter N. Monk Department for Medical Microbiology, Medical School Hannover, Hannover, Germany (A.K., E.W.); and the Department of Infection and Immunity, University of Sheffield Medical School, Sheffield, United Kingdom (K.J.W., P.N.M.) Abstract. ....................................................................................502 I. Introduction. ..............................................................................503 A. Production of Complement Peptides......................................................503 B. Concentrations of Complement Peptides in Health and Disease. .........................503 C. C3a and C5a Generation outside the Complement Cascade ...............................504 D. Deactivation of Complement Peptides ....................................................505 II. The Role of Complement Peptides in Pathophysiology . .....................................505 A. Complement Peptides Are Important Biomarkers of Disease..............................505 B. Functions of the Complement Peptides beyond Innate Immunity .........................506
    [Show full text]
  • Evolution of Prokaryotic Subtilases: Genome-Wide Analysis Reveals Novel Subfamilies with Different Catalytic Residues
    PROTEINS: Structure, Function, and Bioinformatics 67:681–694 (2007) Evolution of Prokaryotic Subtilases: Genome-Wide Analysis Reveals Novel Subfamilies With Different Catalytic Residues Roland J. Siezen,1,2* Bernadet Renckens,1,2 and Jos Boekhorst1 1Center for Molecular and Biomolecular Informatics, Radboud University, Nijmegen, the Netherlands 2NIZO food research, Ede, the Netherlands ABSTRACT Subtilisin-like serine proteases peptides and amino acids for cell growth) or host invasion (subtilases) are a very diverse family of serine pro- (e.g., degradation of host cell–surface receptors or host teases with low sequence homology, often limited enzyme inhibitors), such as the C5a peptidase of Strepto- to regions surrounding the three catalytic resi- coccus pyogenes.6 In recent years it has been shown that dues. Starting with different Hidden Markov Mod- subtilases are also involved in various precursor process- els (HMM), based on sequence alignments around ing and maturation reactions, both intracellularly and the catalytic residues of the S8 family (subtilisins) extracellularly. In prokaryotes, subtilases are known to and S53 family (sedolisins), we iteratively searched be maturation proteases for (i) bacteriocins, such as the all ORFs in the complete genomes of 313 eubacteria lantibiotics,7 (ii) extracellular adhesins, such as filamen- and archaea. In 164 genomes we identified a total tous haemagglutinin,8 and (iii) spore-germination of 567 ORFs with one or more of the conserved enzymes, such as spore-cortex lytic enzyme of Clostrid- regions with a catalytic residue. The large majority ium.9 Subtilases encoded in conserved ESAT-6 gene clus- of these contained all three regions around the ters in mycobacteria, Corynebacterium diphtheriae, and ‘‘classical’’ catalytic residues of the S8 family (Asp- Strepomyces coelicolor are postulated to be involved in His-Ser), while 63 proteins were identified as S53 maturation of secreted T-cell antigens.10 (sedolisin) family members (Glu-Asp-Ser).
    [Show full text]
  • Peptide Sequence
    Peptide Sequence Annotation AADHDG CAS-L1 AAEAISDA M10.005-stromelysin 1 (MMP-3) AAEHDG CAS-L2 AAEYGAEA A01.009-cathepsin D AAGAMFLE M10.007-stromelysin 3 (MMP-11) AAQNASMW A06.001-nodavirus endopeptidase AASGFASP M04.003-vibriolysin ADAHDG CAS-L3 ADAPKGGG M02.006-angiotensin-converting enzyme 2 ADATDG CAS-L5 ADAVMDNP A01.009-cathepsin D ADDPDG CAS-21 ADEPDG CAS-L11 ADETDG CAS-22 ADEVDG CAS-23 ADGKKPSS S01.233-plasmin AEALERMF A01.009-cathepsin D AEEQGVTD C03.007-rhinovirus picornain 3C AETFYVDG A02.001-HIV-1 retropepsin AETWYIDG A02.007-feline immunodeficiency virus retropepsin AFAHDG CAS-L24 AFATDG CAS-25 AFDHDG CAS-L26 AFDTDG CAS-27 AFEHDG CAS-28 AFETDG CAS-29 AFGHDG CAS-30 AFGTDG CAS-31 AFQHDG CAS-32 AFQTDG CAS-33 AFSHDG CAS-L34 AFSTDG CAS-35 AFTHDG CAS-L36 AGERGFFY Insulin B-chain AGLQRGGG M14.004-carboxypeptidase N AGSHLVEA Insulin B-chain AIDIDG CAS-L37 AIDPDG CAS-38 AIDTDG CAS-39 AIDVDG CAS-L40 AIEHDG CAS-L41 AIEIDG CAS-L42 AIENDG CAS-43 AIEPDG CAS-44 AIEQDG CAS-45 AIESDG CAS-46 AIETDG CAS-47 AIEVDG CAS-48 AIFQGPID C03.007-rhinovirus picornain 3C AIGHDG CAS-49 AIGNDG CAS-L50 AIGPDG CAS-L51 AIGQDG CAS-52 AIGSDG CAS-53 AIGTDG CAS-54 AIPMSIPP M10.051-serralysin AISHDG CAS-L55 AISNDG CAS-L56 AISPDG CAS-57 AISQDG CAS-58 AISSDG CAS-59 AISTDG CAS-L60 AKQRAKRD S08.071-furin AKRQGLPV C03.007-rhinovirus picornain 3C AKRRAKRD S08.071-furin AKRRTKRD S08.071-furin ALAALAKK M11.001-gametolysin ALDIDG CAS-L61 ALDPDG CAS-62 ALDTDG CAS-63 ALDVDG CAS-L64 ALEIDG CAS-L65 ALEPDG CAS-L66 ALETDG CAS-67 ALEVDG CAS-68 ALFQGPLQ C03.001-poliovirus-type picornain
    [Show full text]
  • Activation and Inactivation of the Complement Anaphylatoxins
    Activation and Inactivation of the Complement Anaphylatoxins During Chronic Neutrophilic Inflammation of the Cystic Fibrosis Airway Matthew Stott BSc Thesis submitted for the Degree of Doctor of Philosophy September 2018 Institute of Infection and Immunity Cardiff University School of Medicine Heath Park Cardiff CF14 4XN DECLARATION This work has not been submitted in substance for any other degree or award at this or any other university or place of learning, nor is being submitted concurrently in candidature for any degree or other award. Signed ……………………………………………………… (candidate) Date ………………….…………….……… STATEMENT 1 This thesis is being submitted in partial fulfillment of the requirements for the degree of ………(insert MCh, MD, MPhil, PhD etc, as appropriate) Signed ………………………………………….…………… (candidate) Date …………………………….…………… STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated, and the thesis has not been edited by a third party beyond what is permitted by Cardiff University’s Policy on the Use of Third Party Editors by Research Degree Students. Other sources are acknowledged by explicit references. The views expressed are my own. Signed ……………………………………….……….…… (candidate) Date …………………….………………… STATEMENT 3 I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loan, and for the title and summary to be made available to outside organisations. Signed ……………………………………………..…..….. (candidate) Date ………………………………………… STATEMENT 4: PREVIOUSLY APPROVED BAR ON ACCESS I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loans after expiry of a bar on access previously approved by the Academic Standards & Quality Committee.
    [Show full text]
  • All Enzymes in BRENDA™ the Comprehensive Enzyme Information System
    All enzymes in BRENDA™ The Comprehensive Enzyme Information System http://www.brenda-enzymes.org/index.php4?page=information/all_enzymes.php4 1.1.1.1 alcohol dehydrogenase 1.1.1.B1 D-arabitol-phosphate dehydrogenase 1.1.1.2 alcohol dehydrogenase (NADP+) 1.1.1.B3 (S)-specific secondary alcohol dehydrogenase 1.1.1.3 homoserine dehydrogenase 1.1.1.B4 (R)-specific secondary alcohol dehydrogenase 1.1.1.4 (R,R)-butanediol dehydrogenase 1.1.1.5 acetoin dehydrogenase 1.1.1.B5 NADP-retinol dehydrogenase 1.1.1.6 glycerol dehydrogenase 1.1.1.7 propanediol-phosphate dehydrogenase 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) 1.1.1.9 D-xylulose reductase 1.1.1.10 L-xylulose reductase 1.1.1.11 D-arabinitol 4-dehydrogenase 1.1.1.12 L-arabinitol 4-dehydrogenase 1.1.1.13 L-arabinitol 2-dehydrogenase 1.1.1.14 L-iditol 2-dehydrogenase 1.1.1.15 D-iditol 2-dehydrogenase 1.1.1.16 galactitol 2-dehydrogenase 1.1.1.17 mannitol-1-phosphate 5-dehydrogenase 1.1.1.18 inositol 2-dehydrogenase 1.1.1.19 glucuronate reductase 1.1.1.20 glucuronolactone reductase 1.1.1.21 aldehyde reductase 1.1.1.22 UDP-glucose 6-dehydrogenase 1.1.1.23 histidinol dehydrogenase 1.1.1.24 quinate dehydrogenase 1.1.1.25 shikimate dehydrogenase 1.1.1.26 glyoxylate reductase 1.1.1.27 L-lactate dehydrogenase 1.1.1.28 D-lactate dehydrogenase 1.1.1.29 glycerate dehydrogenase 1.1.1.30 3-hydroxybutyrate dehydrogenase 1.1.1.31 3-hydroxyisobutyrate dehydrogenase 1.1.1.32 mevaldate reductase 1.1.1.33 mevaldate reductase (NADPH) 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) 1.1.1.35 3-hydroxyacyl-CoA
    [Show full text]
  • Of Pseudomonas Aeruginosa Mccb 123 and Their Applications
    PROTEASES FROM AN ENVIRONMENTAL ISOLATE OF PSEUDOMONAS AERUGINOSA MCCB 123 AND THEIR APPLICATIONS Thesis submitted to Cochin University of Science and technology in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Enviironmentall Biiotechnollogy Under the Facullty of Enviironmentall Studiies Schooll of Enviironmentall Studiies Cochiin Uniiversiity of Sciience and Technollogy by DIVYA JOSE Reg. No. 3065 NATIONAL CENTRE FOR AQUATIC ANIMAL HEALTH COCHIN UNIVERSITY OF SCIENCE AND TECHNOLOGY KOCHI 682016, KERALA November 2011 This is to certify that the research work presented in the thesis entitled “PROTEASES FROM AN ENVIRONMENTAL ISOLATE OF PSEUDOMONAS AERUGINOSA MCCB 123 AND THEIR APPLICATIONS” is based on the original work done by Ms. Divya Jose (Reg. No. 3065) under the guidance of Dr. A Mohandas, Professor Emeritus, National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Fine Arts Avenue, Kochi -682016 and co- guidance of Dr. I.S Bright Singh, Coordinator, National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Fine Arts Avenue, Kochi- 682016, in partial fulfilment of the requirements for the degree of Doctor of Philosophy and that no part of this work has previously formed the basis for the award of any degree, diploma, associateship, fellowship or any other similar title or recognition. Supervising Guide Co-Guide Dr. A Mohandas Dr. I.S Bright Singh Professor Emeritus, Coordinator, National Centre for Aquatic Animal Health, National Centre for Aquatic Animal Health, CUSAT CUSAT Kochi -682016 Kochi -682016 Kochi-682016 November, 2011 Decllaratiion I hereby do declare that the thesis entitled “PROTEASES FROM AN ENVIRONMENTAL ISOLATE OF PSEUDOMONAS AERUGINOSA MCCB 123 AND THEIR APPLICATIONS” is a genuine record of research work done by me under the guidance of Dr.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,636,359 B2 Kenyon Et Al
    USOO9636359B2 (12) United States Patent (10) Patent No.: US 9,636,359 B2 Kenyon et al. (45) Date of Patent: May 2, 2017 (54) PHARMACEUTICAL COMPOSITION FOR (52) U.S. Cl. TREATING CANCER COMPRISING CPC ............ A61K 33/04 (2013.01); A61 K3I/095 TRYPSINOGEN AND/OR (2013.01); A61K 3L/21 (2013.01); A61K 38/47 CHYMOTRYPSINOGEN AND AN ACTIVE (2013.01); A61K 38/4826 (2013.01); A61 K AGENT SELECTED FROMA SELENUM 45/06 (2013.01) (58) Field of Classification Search COMPOUND, A VANILLOID COMPOUND None AND A CYTOPLASMC GLYCOLYSIS See application file for complete search history. REDUCTION AGENT (75) Inventors: Julian Norman Kenyon, Hampshire (56) References Cited (GB); Paul Rodney Clayton, Surrey U.S. PATENT DOCUMENTS (GB); David Tosh, Bath and North East Somerset (GB); Fernando Felguer, 4,514,388 A * 4, 1985 Psaledakis ................... 424/94.1 Glenside (AU); Ralf Brandt, Greenwith 4,978.332 A * 12/1990 Luck ...................... A61K 33,24 (AU) 514,930 (Continued) (73) Assignee: The University of Sydney, New South Wales (AU) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this KR 2007/0012040 1, 2007 patent is extended or adjusted under 35 WO WO 2009/061051 ck 5, 2009 U.S.C. 154(b) by 0 days. (21) Appl. No.: 13/502,917 OTHER PUBLICATIONS (22) PCT Fed: Oct. 22, 2010 Novak JF et al. Proenzyme Therapy of Cancer, Anticanc Res 25: 1157-1178, 2005).* (86) PCT No.: PCT/AU2O1 O/OO1403 (Continued) S 371 (c)(1), (2), (4) Date: Jun. 22, 2012 Primary Examiner — Erin M Bowers (74) Attorney, Agent, or Firm — Carol L.
    [Show full text]
  • Immunogenicity Assessment of Different Segments and Domains Of
    Article Immunogenicity Assessment of Different Segments and Domains of Group a Streptococcal C5a Peptidase and Their Application Potential as Carrier Protein for Glycoconjugate Vaccine Development Guirong Wang, Jielin Zhao, Yisheng Zhao, Subo Wang, Shaojie Feng and Guofeng Gu * National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, 72 Binhai Road, Qingdao 266237, China; [email protected] (G.W.); [email protected] (J.Z.); [email protected] (Y.Z.); [email protected] (S.W.); [email protected] (S.F.) * Correspondence: [email protected]; Tel.: +86-532-5863-1408 Abstract: Group A streptococcal C5a peptidase (ScpA) is a highly conserved surface virulence factor present on group A streptococcus (GAS) cell surfaces. It has attracted much more attention as a promising antigenic target for GAS vaccine development due to its high antigenicity to stimulate specific and immunoprotective antibodies. In this study, a series of segments of ScpA were rationally designed according to the functional domains described in its crystal structure, efficiently prepared and immunologically evaluated so as to assess their potential as antigens for the development of subunit vaccines. Immunological studies revealed that Fn, Fn2, and rsScpA193 proteins were promising antigen candidates worthy for further exploration. In addition, the potential of Fn and Citation: Wang, G.; Zhao, J.; Zhao, Y.; Fn2 as carrier proteins to formulate effective glycoconjugate vaccine was also investigated. Wang, S.; Feng, S.; Gu, G. Immunogenicity Assessment of Keywords: group A streptococcus; group A streptococcal C5a peptidase; subunit protein vaccine; Different Segments and Domains of immunogenicity; carrier protein Group a Streptococcal C5a Peptidase and Their Application Potential as Carrier Protein for Glycoconjugate Vaccine Development.
    [Show full text]
  • Springer Handbook of Enzymes
    Dietmar Schomburg Ida Schomburg (Eds.) Springer Handbook of Enzymes Alphabetical Name Index 1 23 © Springer-Verlag Berlin Heidelberg New York 2010 This work is subject to copyright. All rights reserved, whether in whole or part of the material con- cerned, specifically the right of translation, printing and reprinting, reproduction and storage in data- bases. The publisher cannot assume any legal responsibility for given data. Commercial distribution is only permitted with the publishers written consent. Springer Handbook of Enzymes, Vols. 1–39 + Supplements 1–7, Name Index 2.4.1.60 abequosyltransferase, Vol. 31, p. 468 2.7.1.157 N-acetylgalactosamine kinase, Vol. S2, p. 268 4.2.3.18 abietadiene synthase, Vol. S7,p.276 3.1.6.12 N-acetylgalactosamine-4-sulfatase, Vol. 11, p. 300 1.14.13.93 (+)-abscisic acid 8’-hydroxylase, Vol. S1, p. 602 3.1.6.4 N-acetylgalactosamine-6-sulfatase, Vol. 11, p. 267 1.2.3.14 abscisic-aldehyde oxidase, Vol. S1, p. 176 3.2.1.49 a-N-acetylgalactosaminidase, Vol. 13,p.10 1.2.1.10 acetaldehyde dehydrogenase (acetylating), Vol. 20, 3.2.1.53 b-N-acetylgalactosaminidase, Vol. 13,p.91 p. 115 2.4.99.3 a-N-acetylgalactosaminide a-2,6-sialyltransferase, 3.5.1.63 4-acetamidobutyrate deacetylase, Vol. 14,p.528 Vol. 33,p.335 3.5.1.51 4-acetamidobutyryl-CoA deacetylase, Vol. 14, 2.4.1.147 acetylgalactosaminyl-O-glycosyl-glycoprotein b- p. 482 1,3-N-acetylglucosaminyltransferase, Vol. 32, 3.5.1.29 2-(acetamidomethylene)succinate hydrolase, p. 287 Vol.
    [Show full text]