Structural heterogeneity and functional differentiation: a rationale for glycosylation analysis of recombinant therapeutics.
Many secreted and membrane-bound proteins exhibit microheterogeneity, even after purification to 'homogeneity'. Posttranslational processing and modification, including glycosylation, often accounts for the observed heterogeneity. While microheterogeneity is traditionally viewed as a biochemical nuisance of little or no functional significance, the increasing weight of recent evidence suggests quite a different perspective: that structural heterogeneity, including microheterogeneity, can impart functional differentiation within the population and thus represents a sophisticated mechanism of biological control and functional diversification. Because of a presumed connection between functional attributes and clinical characteristics, this perspective is the fundamental rationale for the analysis of the glycosylation of proteins employed as therapeutic agents.
Cumming
D A
DA
Carbohydrate Chemistry Group, Genetics Institute, Andover, MA 01810.
D000595:Amino Acid Sequence; D006031:Glycosylation; D015394:Molecular Structure; D011134:Polysaccharides / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D011134:Polysaccharides; D011994:Recombinant Proteins