DOCSLIB.ORG

Using Glycosidases to Remove, Trim, Or Modify Glycans on Therapeutic Proteins

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Using Glycosidases to Remove, Trim, Or Modify Glycans on Therapeutic Proteins February 2016 | Volume 14 | Number 2 www.bioprocessintl.com www.bioprocessintl.com Covering the Whole Development Process for the Global Biotechnology Industry BioProcess International BioProcess FOCUS ON TECHNICAL ARTICLES Vol.14 No.2 February 2016 February No.2 Vol.14 Facing the 483: What to Do? Detecting Impurities: High- Throughput Method Evaluation BridgingUsing Analytical Glycosidases Methods for to Remove, Trim, or Release and Stability TestingEllen P. Guthrie andModifying Paula E. Magnelli Glycans Using Glycosidases Real EstateModify Challenges Glycans in on Therapeutic Proteins Developing Markets Development of a Plant HCP Assay SPECIAL REPORT: CMC Strategy Forum Tackles Process Impurities 14-2-Cover.indd 1 1/13/16 9:59 AM B IOP ROCESS TECHNICAL Using Glycosidases to Remove, Trim, or Modify Glycans on Therapeutic Proteins Ellen P. Guthrie and Paula E. Magnelli ne of the most common Figure 1: Glycoforms identified by LC/MS analysis of intact Erbitux (cetuximab) digested with PNGase F posttranslational modifications of eukaryotic 13.89 Fucose O proteins is glycosylation. 20 Mannose Glycosylation of proteins can affect 18 Sialic acid (NANA) many biological activities. For 16 GlcNAc 15.12 therapeutic glycoproteins, it can 14 Galactose modify biological activity, targeting, 12 Sialic acid (NGNA) trafficking, serum half life, clearance, 10 18.59 and recognition by receptors (1, 2). For (Fluorescence Trace) (Fluorescence 8 6 Or such reasons, biomanufacturers must 10 6 × monitor and characterize the 4 glycosylation patterns of their 19.41 2 11.34 25.02 recombinant therapeutic proteins (3, 4). Counts 9.33 16.37 24.23 27.50 30.99 34.46 37.87 two 0 Therapeutic proteins have 10 15 20 25 30 35 40 main types of glycosylation : N-linked Time (min) glycans and O-linked glycans (5). Attachment of an N-glycan starts in the endoplasmic reticulum (ER), and Golgi apparatus. Host cell and remove, trim, or modify glycans. where a core nascent glycan is linked cell culture conditions can alter the Glycosidases (glycoside hydrolases) through the side-chain amide nitrogen type of N-glycosylation present on the are enzymes that hydrolyze the on specific asparagine residues of a glycoprotein (from high mannose to glycosidic bonds of complex sugars. protein at sites that have the sequence complex and hybrid N-glycans). Such enzymes are applied in three NXS/T, where X can be any amino O-glycosylation occurs in the Golgi main analytical areas for therapeutic acid residue except proline. N-glycans apparatus. N-glycans have a common glycoproteins: removing glycans for are trimmed and further modified as a core consisting of two analysis, trimming glycans for glycoprotein transits through the ER N-acetylglucosamine (GlcNAc) sequencing, and modifying glycans residues and three mannose (Man) in glycoengineering. Herein we PRODUCT FOCUS: RECOMBINANT residues. But the only common core describe the different enzymes used PROTEINS, GLYCOPROTEINS for O-glycans is the N-acetyl- in each area with specific examples galactosamine (GalNAc) residue of their applications. PROCESS FOCUS: PRODUCTION AND attached through the oxygen atom on DOWNSTREAM PROCESSING the side chain of serine or threonine REMOVAL OF GLYCANS FOR ANALYSIS residues of a protein. The most commonly used enzyme for WHO SHOULD READ: PROCESS/PRODUCT Glycosidases: Glycosylation is the removal of N-glycans from a DEVELOPMENT AND ANALYTICS complex and heterogeneic, so multiple glycoprotein is peptide-N-glycosidase KEYWORDS: GLYCOSYLATION, analytical methods must be used to F (PNGase F). It is an amidase that CHROMATOGRAPHY, MASS SPECTROMETRY, determine the structure of glycans and cleaves between the innermost CE-LIF, LC-FLD, ENZYMES their location on a glycoprotein. GlcNAc residue of the N-glycan and Glycosidases are important tools often the asparagine residue that releases LEVEL: INTERMEDIATE used with other analytical methods to the N-glycan. That creates an aspartic Table 1: Substrate specificity of commercially available endoglycosidases ( sialic acid, galactose, mannose, GlcNAc, fucose) the N-glycan core) leaving a GlcNAc Endo- residue attached to the protein. So glycosidase Type of N-Glycans Cleaved Notes Reference they often are used to determine Endo H α 2 α 6 α 6 α α α 6 α 6 14 Endo F1 6 6 α 3 α 6 occupancy or presence of an N-glycan α3 α 2 α 3 α 3 β 4 β 4 α 3 β 4 β 4 α 3 4 β 4β at a specific site. That is particularly α 2 α 2 β 4 β 2 High mannose Hybrid useful for glycoproteins with multiple Endo F2 α 6 N-glycosylation sites. α 2 α 6 α 6 15 α 3 α 3 β 4 β 2 α 2 β 4 β 4 Typically a glycoprotein is digested α 3 β 4 β 4 α 3 α 3 β 4 β 2 α 2 α 2 with an endoglycosidase followed by High mannose Complex biantennary protease cleavage. The peptide Endo F3 β 4 β 2 α 3 fragments are then analyzed using α 6 α 6 β 4 β 2 α 6 15 α 3 β 4 β 2 α 3 MS. The additional mass of a single α 3 β 4 β 4 β 4 β 4 β 4 α 3 β 4 α 3 GlcNAc residue on any peptide α 3 β 2 Complex biantennary β 4 fragment confirms that the site was with core fucosylation Complex triantennary occupied by an N-glycan (6). Because Endo S α 3 Works only b α 3 β 2 16 the site of hydrolysis by endo- -N- β 4 β 2 α 6 α 6 β 4 on IgG Fc β 4 α 6 α 3 β 42 β 4 αβ 62 β 4 acetylglucosaminidases is away from β 4 βα 4 3 α 3 β 4 glycans β 2 α 3 α 3 α 3 β 4 α 3 β 4 the protein backbone, those enzymes β 4 β 4 β 2 often can cleave N-glycans under Complex biantennary with or without a bisecting GlcNAc nondenaturing conditions. That Endo S2 α 6 α 6 17 occurs even when these sites are α 6 Complex biantennary α 3 α 6 α 6 α 3 α 3 refractory to PNGase F cleavage α 3β 4 β 4 α 3 β 4 β 2 β 4 β 4 α 6 β 4 β 4 β 2 under similar native conditions. This High mannose α 3 β 4 β 2 α 3 β 4 Hybrid is especially true for Endo S, which is Endo D α 6 α 6 α 6 18 specific for hydrolysis of N-glycans on β 4 β 4 α 3 α 3 α 3 β 4 β 4 the Fc region of IgG and prefers Paucimannose nondenaturing conditions. The ability Endo M Can also α 6 α 3 19 of such endoglycosidases to hydrolyze α 3 α 6 do trans- β 4 β 4 β 4 β 2 α 3 glycans under native conditions is α 6 α 3 β 4 β 4 glyco- β 4 β 2 Paucimannose sylation especially useful when the goal is to Complex biantennary α 2 reactions α 6 α 6 preserve a protein’s structure. α 2 α 6 α 3 α 3 α 6 α 6 Currently, no known broad α 3 β α 2 β 4 β 4 α 3 β 4 β 4 α 2 β 4 β 2 specificity endoglycosidase can cleave High mannose without Hybrid with all O-glycans from glycoproteins. So core fucosylation bisecting GlcNAc analysis of O-glycans is far more difficult than for N-glycans. Two O-glycosidases are commercially acid residue in place of the asparagine and/or mass spectrometry (LC–MS) available. One is from Streptococcus residue on the protein. or capillary electrophoresis coupled to pneumoniae and can release Core 1 One main reason that glycosidases laser induced fluorescence detection disaccharides consisting of a galactose are so frequently used is that they have (CE–LIF) analysis. Figure 1 (Gal) linked b1–3 to a very broad specificity cleaving high illustrates the variety of N-glycans N-acetylgalactosamine (GalNAc), mannose, complex, and hybrid released from the Erbitux therapeutic where the GalNAc residue is alpha N-glycans. The only limitation for antibody (cetuximab) by PNGase F linked to either a serine or threonine such enzymes is that one cannot and detected by LC–MS analysis. residue of the protein (7). The other cleave if there is an α1–3 fucose linked In addition to PNGase F, many O-glycosidase is from Enterococcus to the core GlcNAc residue (the sugar different endo-b-N-acetylgluco- faecalis and has a slightly broader residue next to the protein). Such saminidases also release N-glycans specificity, cleaving both the Core 1 modification occurs only in plant, from glycoproteins. Most of those disaccharide and the Core 3 insects, mollusks, and parasitic worms. endoglycosidases are limited in the disaccharide that consists of GlcNAc b N-glycans harboring this modification type of N-glycans that they can linked 1–3 to GalNAc (8). can be removed by the enzyme recognize and cleave. Table 1 shows Neither enzyme can cleave if the PNGase A. the different specificities of most disaccharide is further modified by Once an N-glycan has been commercially available endo-b-N- sialic acids or other sugars. Intact released by an amidase, it can be acetylglucosaminidases. All of those O-glycans can be released chemically fluorescently labeled for analysis by endoglycosidases hydrolyze the using b-elimination, but care must be liquid chromatography coupled to N,N′diacetyochitobiose moiety taken with this method not to degrade fluorescence detection (LC–FLD) (between the two GlcNAc residues on the released glycans. Figure 2: Deglycosylation of the etanercept therapeutic protein, a fusion protein with three N-glycans and up to 13 O-glycans: (A) SDS-PAGE gel of etanercept treated with different Another major disadvantage to this combinations of PNGase F and exoglycosidases; lane S is the molecular weight standards.
Load more

Recommended publications
  • A Review of Physiological Effects of Soluble and Insoluble Dietary Fibers
    ition & F tr oo u d N f S o c l i e a n n c r e u s o J Journal of Nutrition & Food Sciences Perry and Ying, J Nutr Food Sci 2016, 6:2 ISSN: 2155-9600 DOI: 10.4172/2155-9600.1000476 Review Article Open Access A Review of Physiological Effects of Soluble and Insoluble Dietary Fibers Perry JR and Ying W* College of Agriculture, Human, and Natural Sciences, 13500 John A Merritt, Tennessee State University, Nashville, TN, USA *Corresponding author: Ying W, College of Agriculture, Human, and Natural Sciences, 13500 John A Merritt, Tennessee State University, Nashville, TN, United States, Tel: 615-963-6006; E-mail: [email protected] Rec date: Feb 18, 2016; Acc date: Mar 03, 2016; Pub date: Mar 14, 2016 Copyright: © 2016 Perry JR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract This paper seeks to characterize the effects of Total Dietary Fibers (TDFs), Soluble Dietary Fibers (SDFs), and Insoluble Dietary Fibers (IDFs) with regard to the rates of digestion, enzymatic activity, the metabolic syndrome, diabetes and glucose absorption, glycemic index, and weight gain. This review intends to narrow pertinent data from the vast body of research, including both in vivo and in vitro experiments. SDF and IDF share a number of the theorized beneficial properties in the diet including weight loss, increased satiety, effects on inflammatory markers, and intestinal microbiota.
    [Show full text]
  • Fructose and Mannose in Inborn Errors of Metabolism and Cancer
    H OH metabolites OH Review Fructose and Mannose in Inborn Errors of Metabolism and Cancer Elizabeth L. Lieu †, Neil Kelekar †, Pratibha Bhalla † and Jiyeon Kim * Department of Biochemistry and Molecular Genetics, University of Illinois, Chicago, IL 60607, USA; [email protected] (E.L.L.); [email protected] (N.K.); [email protected] (P.B.) * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases. Keywords: fructose and mannose; inborn errors of metabolism; cancer Citation: Lieu, E.L.; Kelekar, N.; Bhalla, P.; Kim, J. Fructose and Mannose in Inborn Errors of Metabolism and Cancer.
    [Show full text]
  • Effects of Sugars and Sugar Alcohols on the Gelatinization Temperatures of Wheat, Potato, and Corn Starches
    foods Article Effects of Sugars and Sugar Alcohols on the Gelatinization Temperatures of Wheat, Potato, and Corn Starches Matthew C. Allan, MaryClaire Chamberlain and Lisa J. Mauer * Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA; [email protected] (M.C.A.); [email protected] (M.C.) * Correspondence: [email protected]; Tel.: +1-(765)-494-9111 Received: 13 May 2020; Accepted: 3 June 2020; Published: 8 June 2020 Abstract: The gelatinization temperature (Tgel) of starch increases in the presence of sweeteners due to sweetener-starch intermolecular interactions in the amorphous regions of starch. Different starch botanical sources contain different starch architectures, which may alter sweetener-starch interactions and the effects of sweeteners on Tgels. To document these effects, the Tgels of wheat, potato, waxy corn, dent corn, and 50% and 70% high amylose corn starches were determined in the presence of eleven different sweeteners and varying sweetener concentrations. Tgels of 2:1 sweetener solution:starch slurries were measured using differential scanning calorimetry. The extent of Tgel elevation was affected by both starch and sweetener type. Tgels of wheat and dent corn starches increased the most, while Tgels of high amylose corn starches were the least affected. Fructose increased Tgels the least, and isomalt and isomaltulose increased Tgels the most. Overall, starch Tgels increased more with increasing sweetener concentration, molar volume, molecular weight, and number of equatorial and exocyclic hydroxyl groups. Starches containing more short amylopectin chains, fewer amylopectin chains that span through multiple clusters, higher number of building blocks per cluster, and shorter inter-block chain lengths exhibited the largest Tgel increases in sweetener solutions, attributed to less stable crystalline regions.
    [Show full text]
  • D-Mannose Treatment Neither Affects Uropathogenic Escherichia Coli
    molecules Article d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications 1,2, 3,4, 1 5,6 Daniela Scribano y , Meysam Sarshar y , Carla Prezioso , Marco Lucarelli , 5 1 3,7, 7, , Antonio Angeloni , Carlo Zagaglia , Anna Teresa Palamara y and Cecilia Ambrosi y * 1 Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; [email protected] (D.S.); [email protected] (C.P.); [email protected] (C.Z.) 2 Dani Di Giò Foundation-Onlus, 00193 Rome, Italy 3 Department of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur Italia-Cenci Bolognetti Foundation, 00185 Rome, Italy; [email protected] (M.S.); [email protected] (A.T.P.) 4 Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran 1316943551, Iran 5 Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy; [email protected] (M.L.); [email protected] (A.A.) 6 Pasteur Institute Cenci Bolognetti Foundation, 00161 Rome, Italy 7 IRCCS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy * Correspondence: [email protected]; Tel.: +39-06-4991-4622 These authors contributed equally to this work. y Academic Editor: László Somsák Received: 19 December 2019; Accepted: 10 January 2020; Published: 13 January 2020 Abstract: Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC). Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the emergence of antibiotic resistant strains.
    [Show full text]
  • Ii- Carbohydrates of Biological Importance
    Carbohydrates of Biological Importance 9 II- CARBOHYDRATES OF BIOLOGICAL IMPORTANCE ILOs: By the end of the course, the student should be able to: 1. Define carbohydrates and list their classification. 2. Recognize the structure and functions of monosaccharides. 3. Identify the various chemical and physical properties that distinguish monosaccharides. 4. List the important monosaccharides and their derivatives and point out their importance. 5. List the important disaccharides, recognize their structure and mention their importance. 6. Define glycosides and mention biologically important examples. 7. State examples of homopolysaccharides and describe their structure and functions. 8. Classify glycosaminoglycans, mention their constituents and their biological importance. 9. Define proteoglycans and point out their functions. 10. Differentiate between glycoproteins and proteoglycans. CONTENTS: I. Chemical Nature of Carbohydrates II. Biomedical importance of Carbohydrates III. Monosaccharides - Classification - Forms of Isomerism of monosaccharides. - Importance of monosaccharides. - Monosaccharides derivatives. IV. Disaccharides - Reducing disaccharides. - Non- Reducing disaccharides V. Oligosaccarides. VI. Polysaccarides - Homopolysaccharides - Heteropolysaccharides - Carbohydrates of Biological Importance 10 CARBOHYDRATES OF BIOLOGICAL IMPORTANCE Chemical Nature of Carbohydrates Carbohydrates are polyhydroxyalcohols with an aldehyde or keto group. They are represented with general formulae Cn(H2O)n and hence called hydrates of carbons.
    [Show full text]
  • THE USE of MONOSACCHARIDES, DISACCHARIDES, and TRISACCHARIDES in SYNTHETIC DILUENTS for the STORAGE of RAM SPERMATOZOA at 37°C and 5°C by K
    THE USE OF MONOSACCHARIDES, DISACCHARIDES, AND TRISACCHARIDES IN SYNTHETIC DILUENTS FOR THE STORAGE OF RAM SPERMATOZOA AT 37°C AND 5°C By K. R. LAPWOOD* and 1. C. A. MARTIN* [Manuscript received January 19, 1966] Summary Using synthetic semen diluents based on 20 mM phosphate buffer, 31 mM N aCl, 0·8 % non.dialysable skim milk solids, plus antibiotics, and 185 mM of the sugars ribose, arabinose, xylose, glucose, mannose, fructose, galactose, rhamnose, maltose, lactose, sucrose, or raffinose, it was found that ram spermatozoa survive best at 37°C in diluents containing glucose, mannose, fructose, or sucrose; however, at 5°C ribose, arabinose, xylose, and galactose were the sugars of choice. Increasing replacement of fructose in the diluent with up to 185 mM of these sugars resulted in increased survival at the respective temperatures. Part replacement of 185 mM fructose in the range 7·75-62 mM with the sugars most favourable at 5°C was of little benefit. No effect of changes in osmotic pressure was noted using varying concentrations of the sugars to give tonicities of 0·9, 1· 0, and 1 ·1 relative to 154 mM NaCI or 308 mM sugar. Increased motility scores and percentages of motile sperma· tozoa were observed when 17 mM fructose was added to ribose and arabinose diluents at 5°C, but not when added to diluents containing xylose, the hexoses, galactose, fructose, and glucose; nor for any sugar· containing diluent at 37°C. 1. INTRODUCTION Since the earlier work of Emmens and Blackshaw (1950), who found that the addition of sugars, particularly pentoses, improved revival of mammalian sperma­ tozoa after deep-freezing, viability and fertility studies have shown that the addition of various sugars to semen diluents improve spermatozoal survival at temperatures of approximately 37 and 5°C for the bull, ram, and cock.
    [Show full text]
  • Dietary Fiber: Chemistry, Structure, and Properties
    Journal of Chemistry Dietary Fiber: Chemistry, Structure, and Properties Lead Guest Editor: Ji Kang Guest Editors: Qingbin Guo, Yanjie Bai, and Feng Xu Dietary Fiber: Chemistry, Structure, and Properties Journal of Chemistry Dietary Fiber: Chemistry, Structure, and Properties Lead Guest Editor: Ji Kang Guest Editors: Qingbin Guo, Yanjie Bai, and Feng Xu Copyright © 2018 Hindawi. All rights reserved. This is a special issue published in “Journal of Chemistry.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is prop- erly cited. Contents Dietary Fiber: Chemistry, Structure, and Properties Qingbin Guo, Ji Kang , Yanjie Bai ,andFengXu Editorial (2 pages), Article ID 1328797, Volume 2018 (2018) Relationship of Moisture Status and Quality Characteristics of Fresh Wet Noodles Prepared from Different Grade Wheat Flours from Flour Milling Streams Li Li, Na Wang, Sen Ma , Songzhu Yang, Xuehua Chen, Yingying Ke, and Xiaoxi Wang Research Article (8 pages), Article ID 7464297, Volume 2018 (2018) Effects of Fermented Wheat Bran on Flour, Dough, and Steamed Bread Characteristics Li Li, Zhen Wang, Li-Min Li, Xue-Ling Zheng ,SenMa ,andXiao-XiWang Research Article (7 pages), Article ID 1597308, Volume 2018 (2018) Acetylation Modification Improves Immunoregulatory Effect of Polysaccharide from Seeds of Plantago asiatica L. Le-Ming Jiang ,Shao-PingNie , Dan-Fei Huang, Zhi-Hong Fu, and Ming-Yong Xie Research
    [Show full text]
  • Experiment 20 Identification of Some Carbohydrates
    Experiment 20 Identification of Some Carbohydrates Carbohydrates are the direct product of the photosynthetic combination of carbon dioxide and water. By weight, they are the most common organic compounds on earth. Since most have the empirical formula CnH2nOn = Cn(H2O)n it was initially believed that they were hydrates of carbon. Hence the name. In actuality they are polyhydroxylaldehydes and ketones and exist as cyclic hemi- and full acetals. The cyclic forms may be five-membered rings (furanose) or six-membered rings (pyranose). They are classified as mono-, di-, and polysaccharides. The term sugar applies to mono-, di-, and oligosaccharides, which are all soluble in water and thereby distinguished from polysaccharides, which are not soluble in water. The most commonly encountered carbohydrates are starch, glycogen, inulin, cellulose, sucrose, fructose, arabinose, mannose, glucose, maltose, galactose, and lactose. The method of analysis used in this experiment is one of elimination. The assumption is made that the compound is a single carbohydrate and tests are applied sequentially until a positive result is obtained. The carbohydrate giving the positive test is thus identified. The sugars that we will identify are shown below. Figure 20.1 Monosaccharides Aldohexoses O H C O H CH OH 2 O H C OH C HO OH HO C H HO HO C H OH H C OH HOCH OH HO C H 2 O H C OH D-glucose H C OH HO OH HO H C OH CH2OH D-mannose CH2OH O H C OH H C OH CH2OH CH2OH ketohexose O O C OH HO C H HO HOCH2 O OH HO C H HO C H HO D-galactose H C OH HO H C OH CH2OH CH OH
    [Show full text]
  • Safety Assessment of Microbial Polysaccharide Gums As Used in Cosmetics
    Safety Assessment of Microbial Polysaccharide Gums as Used in Cosmetics Status: Final Report for public distribution Release Date: October 5, 2012 Panel Meeting Date: September 10-11, 2012 The 2012 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D., Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is F. Alan Andersen, Ph.D. This report was prepared by Monice M. Fiume, Senior Scientific Analyst/Writer, and Bart A. Heldreth, Ph.D., Chemist, CIR. Cosmetic Ingredient Review 1101 17th Street, NW, Suite 412 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢ [email protected] ABSTRACT The CIR Expert Panel assessed the safety of 34 microbial polysaccharide gums for use in cosmetics, finding that these ingredients are safe in cosmetic formulations in the present practices of use and concentration. The microbial polysaccharide gums named in this report have a variety of reported functions in cosmetics, including emulsion stabilizer, film former, binder, viscosity increasing agent, and skin conditioning agent. The Panel reviewed available animal and clinical data in making its determination of safety. INTRODUCTION This assessment is a review of information relevant to the safety of 34 microbial polysaccharide gums for use in cosmetic formula- tions. Reported functions for these ingredients include emulsion stabilizer, film former, binder, viscosity increasing agent, and skin conditioning agent.
    [Show full text]
  • D- Mannose to Prevent Recurrent Urinary Tract Infections
    Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2020-037128 on 13 January 2021. Downloaded from D- MannosE to prevent Recurrent urinary tract InfecTions (MERIT): protocol for a randomised controlled trial Marloes Franssen ,1 Johanna Cook,2 Jared Robinson,2 Nicola Williams,2 Margaret Glogowska,2 Yaling Yang,2 Julie Allen,2 Christopher C Butler ,2 Nick Thomas,3 Alastair Hay,4 Michael Moore ,5 Gail Hayward 2 To cite: Franssen M, Cook J, ABSTRACT Strengths and limitations of this study Robinson J, et al. D- MannosE Introduction Recurrent urinary tract infections (RUTIs) to prevent Recurrent urinary have a significant negative impact on quality of life and ► Based on current literature, this will be the first large tract InfecTions (MERIT): healthcare costs. To date, daily prophylactic antibiotics protocol for a randomised publicly funded randomised controlled trial of D- are the only treatment which have been shown to help controlled trial. BMJ Open mannose for prophylaxis of recurrent urinary tract prevent RUTIs. D- mannose is a type of sugar which is 2021;11:e037128. doi:10.1136/ infections. believed to inhibit bacterial adherence to uroepithelial bmjopen-2020-037128 ► This study is the first to use a placebo control in cells, and is already being used by some women in an evaluating the benefit of D- mannose. ► Prepublication history and attempt to prevent RUTIs. There is currently insufficient ► Obtaining the primary outcome by medical notes supplemental material for this rigorous evidence on which to base decisions about its paper is available online. To review will ensure data completeness. use.
    [Show full text]
  • The Immunomodulatory Properties of Β-2,6 Fructans: a Comprehensive Review
    nutrients Review The Immunomodulatory Properties of β-2,6 Fructans: A Comprehensive Review Ian D. Young 1,2,* , Dimitrios Latousakis 1 and Nathalie Juge 1,* 1 Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK; [email protected] 2 Universitätsklinik für Viszerale Chirurgie und Medizin, Inselspital, Bern University Hospital, Department for BioMedical Research (DBMR), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland * Correspondence: [email protected] (I.D.Y.); [email protected] (N.J.) Abstract: Polysaccharides such as β-2,1-linked fructans including inulin or fructose oligosaccharides are well-known prebiotics with recognised immunomodulatory properties. In recent years, other fructan types covering β-2,6-linked fructans, particularly microbial levans, have gained increasing interest in the field. β-2,6-linked fructans of different degrees of polymerisation can be synthesised by plants or microbes including those that reside in the gastrointestinal tract. Accumulating evidence suggests a role for these β-2,6 fructans in modulating immune function. Here, we provide an overview of the sources and structures of β-2,6 fructans from plants and microbes and describe their ability to modulate immune function in vitro and in vivo along with the suggested mechanisms underpinning their immunomodulatory properties. Further, we discuss the limitations and perspectives pertinent to current studies and the potential applications of β-2,6 fructans including in gut health. Keywords: fructan; levan; immunomodulatory; microbiota; gut health; immunity; fructose; polysac- Citation: Young, I.D.; Latousakis, D.; charide; fructooligosaccharide; exopolysaccharide Juge, N. The Immunomodulatory Properties of β-2,6 Fructans: A Comprehensive Review.
    [Show full text]
  • Method for Concentrating Mannose in Aqueous Glucose Solutions
    Europaisches Patentamt © J European Patent Office © Publication number: 0 074 713 Office europeen des brevets A1 EUROPEAN PATENT APPLICATION © Application number: 82304164.5 ©lnt.CI»: C 13 K 13/00 C 07 C 29/10 © Date of filing: 06.08.82 ©Priority: 14.09.81 US 301728 ©Applicant: ICI AMERICAS INC Concord Pike & New Murphy Road Wilmington Delaware 19897(US) © Date of publication of application: 23.03.83 Bulletin 83/12 © Inventor: Kruse, Walter Frank 1 Woodbury Court © Designated Contracting States: Wilmington Delaware 19805(US) BE FR GB IT © Inventor: de Berardinis, Albert Joseph 113 Sherbrooke Drive Wilmington Delaware 19808(US) © Representative: Aufflick, James Neil et al, Imperial Chemical Industries PLC Legal Department: Patents Thames House North Millbank London SW1P4QG(GB) © Method for concentrating mannose in aqueous glucose solutions. Glucose is separated from an aqueous solution contain- ing glucose and mannose by saturating said solution with sodium halide to form an insoluble sodium halide/glucose hydrate adduct which is precipitated. The mannose rich solutions are subsequently demineralized and reduced by hydrogenation to produce mannitol/sorbitol concentrates wherein the ratio of mannitol to sorbitol is at least 1/1. This invention relates to a method for concentrating mannose in aqueous solutions containing glucose and to a semi- continuous process for preparing high concentrations of mannose comprising the steps of epimerizing glucose to aqueous solutions containing glucose and mannose, precipating a sodium halide adduct, of glucose hydrate to yield a filtrate rich in mannose, and separ- ating the excess sodium halide from the filtrate. The glucose hydrate adduct can be recycled to the epimerization step for further conversion to mannose.
    [Show full text]