Covalent bonds, protein-based

Whereas DNA is a relatively simple polyanion and can be modified and easily immobilized on solid surfaces based on electrostatic interactions or covalent bonding, protein bonding is much more delicate. The complexity derives from a multitude of biochemical properties. Protein molecules possess particular three-dimensional structures and varying chemical and physical properties (e.g., hydrophilic and hydrophobic domains, ionic interactions), and the activity and function as well as the partial charge of domains depend on the local physical and chemical microenvironment. Additionally, complexity is further increased by posttranscriptional modifications of protein conformation hence the well-established on-chip approaches of oligonucleotide microarrays are not applicable to protein microarrays. For protein microarray production, four major requirements have to be fulfilled ... 

Alkylating agent, a reactive chemical that forms a covalent bond with chemical moieties on the biological target (usually a protein). For instance, p-haloalkylamines generate an aziridinium ion in aqueous base that inserts into -SH, -CHOH, or other chemical structures in peptides. Once inserted, the effects of the alkylating agent are irreversible. 

Figure 5.37 APG can be used to label specifically arginine residues in proteins, producing stable, cyclic Schiff base-like bonds with the side-chain guanidino groups. Photoactivation with UV light then causes ring expansion of the phenyl azide group, initiating covalent bond formation with amines.

The rational synthesis of peptide-based nanotubes by self-assembling of polypeptides into a supramolecular structure was demonstrated. This self-organization leads to peptide nanotubes, having channels of 0.8 nm in diameter and a few hundred nanometer long (68). The connectivity of the proteins in these nanotubes is provided by weak bonds, like hydrogen bonds. These structures benefit from the relative flexibility of the protein backbone, which does not exist in nanotubes of covalently bonded inorganic compounds. 

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