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DOI: 10.1055/s-0035-1560520
Solid-Phase-Based Synthesis of Ureidopyrimidinone–Peptide Conjugates for Supramolecular Biomaterials
Publication History
Received: 14 August 2015
Accepted after revision: 13 October 2015
Publication Date:
03 November 2015 (online)
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Abstract
Supramolecular polymers have shown to be powerful scaffolds for tissue engineering applications. Supramolecular biomaterials functionalized with ureidopyrimidinone (UPy) moieties, which dimerize via quadruple hydrogen-bond formation, are eminently suitable for this purpose. The conjugation of the UPy moiety to biologically active peptides ensures adequate integration into the supramolecular UPy polymer matrix. The structural complexity of UPy–peptide conjugates makes their synthesis challenging and until recently low yielding, thus restricted the access to structurally diverse derivatives. Here we report optimization studies of a convergent solid-phase based synthesis of UPy-modified peptides. The peptide moiety is synthesized using standard Fmoc solid-phase synthesis and the UPy fragment is introduced on the solid-phase simplifying the synthesis and purification of the final UPy–peptide conjugate. The convergent nature of the synthesis reduces the number of synthetic steps in the longest linear sequence compared to other synthetic approaches. We demonstrate the utility of the optimized route by synthesizing a diverse range of biologically active UPy–peptide bioconjugates in multimilligram scale for diverse biomaterial applications.
1 Introduction
2 Divergent Synthesis
3 Convergent Synthesis
4 UPy–Amine Strategy
5 UPy–Carboxylic Acid Strategy
6 Conclusion
Key words
modular approach - quadruple hydrogen bonding - peptides - solid phase - biofunctionalization - bioactive materialsSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560520.
- Supporting Information
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References and Notes
- 1 These authors contributed equally.
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