Material–peptide pair interactions have found applications as interfaces and connectors to metal surfaces, as templates to control size and crystal phase of semiconductors and for synthesis of orientated assemblies of materials. These polymer-peptide interactions also have been exploited for cell-adhesion enhancement, non-fouling surfaces, the control of drug release and the desired protein collection. In this study, a general procedure for identifying matched affinity pairs of peptides and synthetic copolymer hydrogel nanoparticles (NPs) is described. A phage library was used to present a large (&gt; 10<sup>10</sup>) number of linear and cyclic peptides to NPs with discrete chemical compositions. Most peptide sequences had little or no affinity for the synthetic polymers. However, phage selection by the NP and sequencing provided a small number of peptides with high affinity for the synthetic copolymer hydrogel. The affinity was quantitatively evaluated by quartz crystal microbalance (QCM). A 12 amino acid cyclic peptide with approximately 23 nM affinity for a NIPAm based hydrogel nanoparticle copolymer was selected. Binding studies of the cyclic and linear forms of the peptide established that NP affinity was significantly influenced by peptide conformation. The cyclic form, that which was presented in the selection process, had &gt;3 times higher affinity for the NP compared to the linear form. Affinity studies of series of single and multiple point mutations of the peptide established NP affinity for the peptide was based not only upon peptide conformation but also the specific sequence of amino acids in the peptide chain with both hydrophobic and electrostatic interactions contributing to binding. The results establish a general method for discovery of high affinity selective synthetic hydrogel copolymer-peptide affinity pairs, insight into the molecular details of these interactions and the potential for utilizing these affinity pairs in applications that range from biomacromolecule purification to therapeutics.

Mining for peptides with affinity for a synthetic copolymer hydrogel nanoparticle: Compositional and structural contributions to affinity

2019 Fall National Meeting

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