PEGYLATION AND ACYLATION
In the last years therapeutic proteins have been intensively used for the treatment of several diseases, like chronic hepatitis and cancer. However, a lot of these proteins show undesirable properties as:
- short plasma half life
- immunogenic response generation
- fast proteolytic degradation
- poor solubility
- poor stability
With the aim of solving these disadvantages, some strategies that improve pharmacokinetic and pharmacodynamics properties of therapeutic proteins have been proposed. The most attractive and used technologyis the covalent attachment of fatty acids or synthetic or natural polymers like polyethyleneglycol (PEG), commonlyknown as pegylation or conjugation.
PEG is a lineal or branched poliether that is widely used in pharmaceutical formulations. Moreover, PEG is frequently employed in human pharmaceutical field since is:
- A biocompatible synthetic polymer
- Low costs
- Non toxic
- Non immunogenic
When PEG is correctly attached to biomolecules (process known as pegylation), the biomolecule keeps its bioactivity (enzymatic activities, receptor recognition, target sequence recognition, and signal trigger) while PEG change some of its physicochemical properties:
• Enhancement of apparent volume which reduces clearance altering biodistribution
• Masking of antigenic areas, diminishing immunologic response
• Modification of degradation rate by proteolytic enzymes
Conjugation of therapeutic proteins with PEG or fatty acids is technologically complexand it needsto use active derivatives that react with biomolecules in a mild and selective way to prevent modification of biological activity.
Using our own technology, Laboratorio Horian I+D is dedicated to produce lineal and branched activated PEG derivatives with high quality. We are also capable of activating fatty acids.Those active reagentsare used in pegylation/acylation of several therapeutic proteins.
In Laboratorio Horian I+D we have abilities to integrally deal with diverse challenges presented in pegylation/acylation technology, including:
• Chemical modification of linear and branched PEGs with several functional groups and linkers
• Purification of activated PEGs derivatives and fatty acids
• PEGs and fatty acids conjugation with biomolecules
• Purification technology of pegylated/acylated products
• Quality control andmonitoring methods of each stepin processes.
• Design of productive facility layout and scaling up of each step involved in the production ofchemically modified biomolecules.
• WO 2012003045 A2 – “Process for the preparation of poly (alkylene oxide) derivatives for modification of biologically active molecules and materials” Vaillard S.E., Gonz´lez M., Grau R.J.A. App Num. PCT/US2011/035733.
• AR082034 A1.“Proceso para la preparación de derivados de óxidos de polialquileno para la modificación de moléculas y materiales biológicamente activos”. González M., Grau R.J.A., Vaillard S.E.
• “Method for the synthesis of N-alkyl-O-alkyl carbamates”. Vaillard V.A., González M., Perotti J.P., Grau R.J.A, Vaillard S.E. RSC Advances (IF 2.526). 4,13012-13017. ISSN: 2046-2069. March 2014.
• “Evolution of Reactive mPEG Polymers for the Conjugation of Peptides and Proteins”. González M., Vaillard S.E. Current Organic Chemistry (IF 3.222).Vol 17 (9), 975-998. ISSN: 1385-2728 (Print), 1875-5348 (Online). June 2013.
• “New method for the synthesis and purification of branched mPEG2Lys”. González M., Grau R. J. A., Vaillard S. E. Reactive and functional polymers (Elsevier) (IF 2.505). Vol: 72, 107-113. ISSN: 1381-5148. October 2011.
• “Pegylation: an overview and recent advances reported in the patent literature”. González M., Vaillard S. E., Grau R. J. A. Recent Patents on Chemical Engineering. Vol 4; 241-264. ISSN: 2211-3347 (Print); 1874-4788 (Online). June 2011.