Biology Reference
In-Depth Information
therapeutic molecules can be linked to VNPs in order to generate “smart”
devices for targeted drug delivery (discussed in Chapter 8). For potential
applications in novel materials, conducting materials have been chemically
linked to VNPs to create nanocircuits, which may be useful for novel
nanoelectronic devices. VNPs have also been applied as sensors and have
been developed for light-harvesting systems (discussed in Section 4.4).
Nearly any chemical compound or functional molecule can be covalently
linked to VNPs; hence, the potential applications of VNPs are open-ended.
This chapter will provide an overview of the different bioconjugation
chemistries that have been applied to a variety of VNP building blocks.
These protocols range from standard labeling protocols using commercially
available compounds to advanced chemistries such as click chemistry
and diazonium coupling strategies. For general background reading on
bioconjugation techniques, the following textbooks are recommended:
Bioconjugate Techniques
(Hermanson, 1996) and
Bioconjugation
(Aslam &
Dent, 1999).
.1 oVerVIeW: AddreSSABle SurFACe grouPS
The capsids of VNPs are composed of many identical copies of coat proteins,
which consist of amino acids. Amino acids serve as targets for bioconjugation
chemistry. Some viruses are glycosylated and the carbohydrates may also be
utilized for functionalization (see Section 4.1.5).
There are 20 common amino acids found in proteins (Fig. 4.1). Each
amino acid contains an amino group and a carboxylate attached to a central
carbon atom, the
-carbon, and a side chain. The side chain is different
and characteristic for each of the 20 common amino acids. The amino and
carboxylate groups attached to the
α
-carbon participate in the formation
of the peptide bond that links amino acids together to form a peptide or
protein. The side chains do not participate in the formation of the covalent
peptide bond and are thus available for bioconjugation. Whether a particular
amino acid side chain on a VNP can serve as a target for functionalization
depends on (i) the location on the viral capsid and (ii) the microenvironment
of the side chain. Amino acids that are solvent-exposed on either the exterior
or interior surface of the capsid are generally available for modification
protocols. However, the reactivity of a specific residue also depends on the
microenvironment, as some side chains participate in interactions with
neighboring side chains and therefore may not be accessible for chemical
bioconjugation. Common interactions include electrostatic interactions,
hydrogen bonding, and, for Cys side chains, covalent disulfide bonds.
α
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