Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

Chelsea L Rintelmann; Tara Grinnage-Pulley; Kathleen Ross; Daniel E K Kabotso; Angela Toepp; Anne Cowell; Christine Petersen; Balaji Narasimhan; Nicola Pohl

doi:10.3762/bjoc.15.58

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Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

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Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

Chelsea L Rintelmann, Tara Grinnage-Pulley, Kathleen Ross, Daniel E K Kabotso, Angela Toepp, Anne Cowell, Christine Petersen, Balaji Narasimhan and Nicola Pohl

Beilstein journal of organic chemistry, Vol.15(1), pp.623-632

03/11/2019

DOI: 10.3762/bjoc.15.58

PMCID: PMC6423605

PMID: 30931004

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Abstract

Leishmaniasis, a neglected tropical disease, currently infects approximately 12 million people worldwide with 1 to 2 million new cases each year in predominately underdeveloped countries. The treatment of the disease is severely underdeveloped due to the ability of the Leishmania pathogen to evade and abate immune responses. In an effort to develop anti-leishmaniasis vaccines and adjuvants, novel carbohydrate-based probes were made to study the mechanisms of immune modulation. In this study, a new bioerodible polyanhydride microparticle was designed and conjugated with a glycodendrimer molecular probe. This molecular probe incorporates a pathogen-like multivalent display of α-1,2-trimannose, for which a more efficient synthesis was designed, with a tethered fluorophore. Further attachment of the glycodendrimer to a biocompatible, surface eroding microparticle allows for targeted uptake and internalization of the pathogen-associated oligosaccharide by phagocytic immune cells. The α-1,2-trimannose-linked bioerodible microparticles were found to be safe after administration into the footpad of mice and demonstrated a similar response to α-1,2-trimannose-coated latex beads during L. major footpad infection. Furthermore, the bioerodible microparticles allowed for investigation of the role of pathogen-associated oligosaccharides for recognition by pathogen-recognition receptors during L. major- induced leishmaniasis.

adjuvant

carbohydrates

Chemistry

Full Research Paper

L. major

microparticle

PAMP

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Title: Subtitle: Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection
Creators: Chelsea L Rintelmann - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Tara Grinnage-Pulley - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Kathleen Ross - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Daniel E K Kabotso - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Angela Toepp - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Anne Cowell - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Christine Petersen - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Balaji Narasimhan - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Nicola Pohl - Department of Chemistry, Indiana University Bloomington, 800 E. Kirkwood Ave., Bloomington, Indiana 47405-7102, USA Department of Epidemiology, College of Public Health, University of Iowa, 105 River Street, S444 CPHB, Iowa City, Iowa 52242, USA Center for Emerging Infectious Diseases, University of Iowa Research Park, 2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall, Ames, Iowa 50011-2230, USA Department of Chemical and Biological Engineering, Iowa State University, 618 Bissell Road, Ames, Iowa 50011-2230, USA
Resource Type: Journal article
Publication Details: Beilstein journal of organic chemistry, Vol.15(1), pp.623-632
DOI: 10.3762/bjoc.15.58
PMID: 30931004
PMCID: PMC6423605
NLM abbreviation: Beilstein J Org Chem
ISSN: 1860-5397
eISSN: 1860-5397
Publisher: Beilstein-Institut
Language: English
Date published: 03/11/2019
Academic Unit: Epidemiology; Internal Medicine
Record Identifier: 9984214716902771

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