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Proefschrift

Self adjuvanting immunopeptides: Design and synthesis

Chapter 2 describes a post-synthetic methodology to introduce a fluorescent label in highly lipophilic, Pam3Cys based conjugates.

Auteur
Gential, G.P.P.
Datum
17 december 2018
Links
Thesis in Leiden Repository

Chapter 2 describes a post-synthetic methodology to introduce a fluorescent label in highly lipophilic, Pam3Cys based conjugates. The fluorescent labels were appended to the peptide part of the conjugate with the aid of a strain promoted [3+2] azide-alkyne cycloaddition. In Chapter 3 a synthesis is discussed of a structurally simple human specific TLR-2 ligand with diminished lipophilicity, as compared to Pam3Cys. Conjugation of such moiety to peptide is studied and optimized to produce human specific analogues of the conjugates described in Chapter 2 with higher solubility and an equal propensity to activate TLR-2. The synthesis of a newly designed TLR-7 agonist is demonstrated in Chapter 4 as well as the synthesis of a selection of self-adjuvanting immunogenic peptides that contain a model MHC-I epitope (SIINFEKL). A biocompatible methodology to reduce an azide in a side chains of peptides is described in Chapter 5 with a particular focus on side reaction occurring during the reduction. A selection of phosphines is evaluated under biocompatible aqueous conditions. 6 describes the development of a convergent synthesis of the naturally occurring conjugate between the 5’- terminal fragment of genomic RNA from Coxsackie virus and the full-length viral genome-linked protein (VPg).

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