Title:Conjugative Post-Translational Modifications for Pharmacological Improvement of Therapeutic Proteins
VOLUME: 15 ISSUE: 1
Author(s):Diego de Carvalho Carneiro* and Suzana Telles da Cunha Lima
Affiliation:Department of Biointeraction, Institute of Health Sciences, Federal University of Bahia, Salvador, Department of General Biology, Institute of Biology, Federal University of Bahia, Salvador
Keywords:Biopharmaceuticals, fatty acylation, glycosylation, PEGylation, pharmacology, PTMs.
Abstract:Therapeutic proteins can be pharmacologically improved by conjugative post-translational
modifications through the rational design of their structure and production process. N- and O- linked
glycosylation can confer advantages to proteins and can be controlled by the process conditions, producing
cell lines and enzymatic expression or activity. The resulting glycan profile influences their
pharmacological features such as in the biopharmaceutical velaglucerase alfa. Conjugation of polyethylene
glycol onto therapeutic proteins has been used to overcome pharmacological limitations. They
can be site-specifically or randomly linked through the reaction between a terminal group of the polyethylene
glycol molecule and an amino acid residue group of the protein. Both components (protein
and polyethylene glycol) participate in pharmacological mechanisms, enabling a longer half-life for
peginterferon beta-1a, for example. Fatty acylation of proteins occurs in cells via some known reactions
that may involve different linkages, fatty acids, modified residues, and enzymes. Insulin degludec
is a fatty acylated biopharmaceutical formulated to solve the problem of variability in insulin exposure
associated with other products. Conjugative post-translational modifications can be used to pharmacologically
improve even therapeutic proteins produced by prokaryotic cell lines while exploring them
may result in the development of other potential uses as well as new generations of biopharmaceuticals.
