Mass spectrometry study of a transferrin-based protein drug reveals the key role of protein aggregation for successful oral delivery

Bobst C.E.; Wang S.; Shen W.-C.Kaltashov I.A.

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Mass spectrometry study of a transferrin-based protein drug reveals the key role of protein aggregation for successful oral delivery

机译：Mass spectrometry study of a transferrin-based protein drug reveals the key role of protein aggregation for successful oral delivery

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A recently designed human growth hormone/transferrin fusion protein (GHT) remains one of the very few examples of a protein capable of eliciting measurable therapeutic response after oral administration. To better understand the underlying factors that resulted in this rare success of nonparenteral protein drug delivery, we analyzed proteolytic stability and receptor binding properties of this protein, the key factors in overcoming the primary barriers to successful oral delivery. Analysis of GHT by a combination of size exclusion chromatography and mass spectrometry revealed that a significant protein population exists in an oligomeric (GHTx) state in addition to the anticipated monomer (GHT1). These states of GHT were evaluated for their survivability in stomach-like conditions, as well as their ability to bind transferrin receptor (TfR). Our results reveal an exceptional stability of GHTx, as well as the preserved ability to bind TfR, a critical first step in crossing the epithelial-intestinal barrier through receptor-mediated transcytosis.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第34期|13544-13548|共5页
作者
Bobst C.E.; Wang S.; Shen W.-C.Kaltashov I.A.;
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作者单位

Department of Chemistry, University of Massachusetts, Amherst, MA 01003, United States;

Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Electrospray ionization; Native electrospray ionization MS; Protein therapeutic; Protein/receptor interaction; Recombinant fusion protein;

Mass spectrometry study of a transferrin-based protein drug reveals the key role of protein aggregation for successful oral delivery

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