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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. Rintelmann1, Tara Grinnage-Pulley2,3,4, Kathleen Ross4,5,
Daniel E. K. Kabotso1, Angela Toepp2,3, Anne Cowell1, Christine Petersen*2,3,4,
Balaji Narasimhan*4,5 and Nicola Pohl*1,4
Full Research Paper
Address:
Beilstein J. Org. Chem. 2019, 15, 623–632.
1Department of Chemistry, Indiana University Bloomington, 800 E.
Kirkwood Ave., Bloomington, Indiana 47405-7102, USA, 2Department
of Epidemiology, College of Public Health, University of Iowa, 105
River Street, S444 CPHB, Iowa City, Iowa 52242, USA, 3Center for
Emerging Infectious Diseases, University of Iowa Research Park,
2500 Crosspark Road, MTF B166 Coralville, Iowa 52241, USA,
4Nanovaccine Institute, Iowa State University, 2114 Sweeney Hall,
Ames, Iowa 50011-2230, USA and 5Department of Chemical and
Biological Engineering, Iowa State University, 618 Bissell Road,
Ames, Iowa 50011-2230, USA
doi:10.3762/bjoc.15.58
Received: 26 November 2018
Accepted: 20 February 2019
Published: 11 March 2019
Associate Editor: D. Spring
© 2019 Rintelmann et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Email:
* Corresponding author
Keywords:
adjuvant; carbohydrates; L. major; microparticle; PAMP
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.
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