Development of CE methods to analyze potential components of the angiogenic glycoprotein vascular endothelial growth factor 165
2009 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 30, no 2, 315-324 p.Article in journal (Refereed) Published
The vascular endothelial growth factor 165 (VEGF165) is the predominant form of thecomplex VEGF family. This glycoprotein has, among others, an angiogenic effect inmany physiological and pathological events. For this reason, its roles as a biomarker andas a therapeutic drug have been considered. However, very little is known about theexistence of different forms of VEGF165 arising from glycosylation and other potentialPTMs. This aspect is crucial because it is known that for other glycoproteins the ratiobetween these isoforms actually acts as a biomarker for certain diseases and otherphysiological states. In addition, for therapeutic use of glycoproteins it is known that thebiological activity may differ for the various isoforms. In this work CE methods toseparate up to seven peaks without baseline resolution containing various forms ofVEGF165 are developed. Using a computer program previously developed in-house peakassignment could be performed with accuracy close to 100%. In this way, comparisonbetween recombinant human VEGF165 expressed in insect cells, which is a glycosylatingsystem, and in Escherichia coli cells, which are unable of performing glycosylation ofproteins, has been possible. The methods developed, besides providing informationabout the existence of several forms of VEGF165, mean a starting point that permits thestudy of the role of VEGF165 as a potential biomarker of different diseases and physiologicalprocesses and to perform quality control of the recombinant drug duringmanufacturing. To the best of our knowledge this is the first time that CE methods forVEGF165 have been developed.
Place, publisher, year, edition, pages
2009. Vol. 30, no 2, 315-324 p.
Angiogenesis, Biomarker, Glycoprotein, Isoform / VEGF
Research subject Analytical Chemistry
IdentifiersURN: urn:nbn:se:uu:diva-100697DOI: 10.1002/elps.200800140ISI: 000263708900003PubMedID: 19204948OAI: oai:DiVA.org:uu-100697DiVA: diva2:210814