Synthesis of mannosylated lipopeptides with receptor targeting properties

Sedaghat, Bita, Stephenson, Rachel J., Giddam, Ashwini Kumar, Eskandari, Sharareh, Apte, Simon H., Pattinson, David J., Doolan, Denise L. and Toth, Istvan (2016) Synthesis of mannosylated lipopeptides with receptor targeting properties. Bioconjugate Chemistry, 27 3: 533-548. doi:10.1021/acs.bioconjchem.5b00547

Author Sedaghat, Bita
Stephenson, Rachel J.
Giddam, Ashwini Kumar
Eskandari, Sharareh
Apte, Simon H.
Pattinson, David J.
Doolan, Denise L.
Toth, Istvan
Title Synthesis of mannosylated lipopeptides with receptor targeting properties
Journal name Bioconjugate Chemistry   Check publisher's open access policy
ISSN 1520-4812
Publication date 2016-01-06
Sub-type Article (original research)
DOI 10.1021/acs.bioconjchem.5b00547
Open Access Status Not Open Access
Volume 27
Issue 3
Start page 533
End page 548
Total pages 16
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2017
Language eng
Formatted abstract
Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front line receptor in pathogen recognition. During the past decade many attempts have been made to target this receptor for applications including vaccine and drug development. In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4+ epitope, OVA323−339, as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. Uptake studies performed on F4/80+ and CD11c+ cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the control peptides (peptide with no lipid and peptide with no mannose and no lipid). Furthermore, mannan inhibition assays demonstrated that uptake of the mannosylated and lipidated peptides was receptor mediated. To address the specificity of receptor uptake, surface plasmon resonance studies were performed using biacore technology and confirmed high affinity of the mannosylated and lipidated vaccine constructs toward the MR. These studies confirm that both mannose and lipid moieties play significant roles in receptor-mediated uptake on APCs, potentially facilitating vaccine development.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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Created: Mon, 22 Feb 2016, 10:31:39 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences