Synthesis of Phospho-Amino Acid Analogues as Tissue Adhesive Cement Additives

Christopher D Spicer; Michael Pujari-Palmer; Hélène Autefage; Gerard Insley; Philip Procter; Håkan Engqvist; Molly M Stevens

doi:10.1021/acscentsci.9b01149

Synthesis of Phospho-Amino Acid Analogues as Tissue Adhesive Cement Additives

ACS Cent Sci. 2020 Feb 26;6(2):226-231. doi: 10.1021/acscentsci.9b01149. Epub 2020 Feb 11.

Authors

Christopher D Spicer^{1

2

3}, Michael Pujari-Palmer⁴, Hélène Autefage¹, Gerard Insley⁴, Philip Procter⁴, Håkan Engqvist⁴, Molly M Stevens^{1

5}

Affiliations

¹ Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
² Department of Chemistry, University of York, Heslington YO10 5DD, United Kingdom.
³ York Biomedical Research Institute, University of York, Heslington YO10 5DD, United Kingdom.
⁴ Applied Material Science, Department of Engineering, Uppsala University, 75121 Uppsala, Sweden.
⁵ Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom.

Abstract

In this paper we report the synthesis of a library of phospho-amino acid analogues, via a novel single-step allyl-phosphoester protection/Pd-mediated deprotection strategy. These phosphoserine and phosphotyrosine analogues were then applied as additives to create adhesive calcium phosphate cements, allowing us to probe the chemical origins of the increased surface binding strength. We demonstrate the importance of multiple calcium binding motifs in mediating adhesion, as well as highlighting the crucial role played by substrate hydrophobicity and orientation in controlling binding strength.