Hybrid biomaterials based on synthetic (polymer) and biological (proteins, peptides) building blocks, called protein-polymer conjugates, provide a range of opportunities for man-made materials to interface with biological system at the molecular level [1]. Encoded by their amino acid sequence, peptides form secondary structures (alpha-helices, beta-sheets) which self-assemble into tertiary structures such as coiled-coil bundles or beta-barrels in a hierarchical manner. For therapeutics, polymer functionalization, often by poly(ethylene glycol), PEG (“PEGylation”), is an effective method to improve the solubility, increase the life time and protect the proteins from the immune system [2]. It is therefore essential to investigate the integrity of the structures, and in particular address the conformation of the polymer chains in situ In this work we consider two families of peptides that are able to form alpha-helical (coiled-coil) bundles [3,4] and beta-sheet fibrils respectively [5]. We show how small-angle X-ray scattering (SAXS) can be efficiently used to characterize detailed structural features including the polymer chain conformation. We will provide an overview of the methodology, specifically addressing model peptides that self-assemble into tertiary structures and relate their solution structure to their crystallographic structure. Particular attention will be given to the effect of PEG and the modification of polymer conformation when attached to the peptides. We will also discuss lipid-modified peptides that form micellar structures.
References
1. R. Duncan 2006. Nat Rev Cancer 6(9):688–701.
2. JM. Harris and RB. Chess 2003.. Nat Rev Drug Discov 2(3):214–221.
3. J. Shu J, R. Lund and T. Xu 2012 Biomacromolecules 13(6): 1945–1955.
4. R. Lund, J., Shu and T. Xu 2013 Macromolecules 46(4):1625–1632
5. M. Yang, D. Xu, L. Jiang, D. Dustin, R. Lund and H. Dong Chem. Commun. 2014.
reidar.lund@kjemi.uio.no
