Bioconjugates: The Adaptable Challenge

Conjugation of a biologic to a carrier molecule can solve problems in solubility and stability, but introduces its own set of challenges.
Jan 01, 2013
Volume 26, Issue 1

Trishul Shah
With the advent of whole-genome sequence projects, a wealth of information has been attained and continues to be acquired about biomolecules and their biological processes. The information has led to the discovery of numerous new peptide and protein therapeutics based on these entities; however, there a number of challenges facing potential therapeutics that include delivery, compliance, and half-life. The burgeoning field of bioconjugation provides a route to overcoming some of these challenges.

Bioconjugation is the covalent derivatization of biomolecules such as protein, peptides, oligonucleotides, and antibodies. Bioconjugates are gaining popularity because of their versatility in a number of applications. Bioconjugates, such as fluorescent molecules and biotin, can be used as probes and diagnostic aids for imaging. Larger conjugates, such as polyethyleneglycol (PEG), are being used in therapeutic areas to enhance water solubility, reduce immunogenicity, and increase in vivo circulation half-life.

Most peptides composed of naturally occurring L-amino acids have short half-lives, often measured in minutes in vivo. Considerable effort has been invested in stabilizing peptidic drug substances either by chemical modification or by incorporating the peptide into a matrix that slowly releases the pharmaceutical active into its environment. Chemical modification by introduction of D- and exotic amino acids, as well as C- and N-terminal capping, are still viable techniques for protecting peptides from enzymatic degradation. The use of conjugation agents such as PEGs, however, has also been used successfully for extending the half-life of proteins and peptides by preventing enzymatic degradation and renal clearance (1, 2). The half-life of bioconjugates is dependent on the in vivo rate of degradation of the conjugate (i.e., PEG, HES, XTEN, or HSA), and therefore, for any given dosage, the half-life of the bioconjugate cannot be longer than the half-life of the polymer itself.