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Potency and stability of C terminal truncated human epidermal growth factor

Citation

Calnan, DP and Fagbemi, A and Berlanga-Acosta, J and Marchbank, T and Sizer, T and Lakhoo, K and Edwards, AD and Playford, RJ, Potency and stability of C terminal truncated human epidermal growth factor, Gut: An International Journal of Gastroenterology and Hepatology, 47, (5) pp. 622-627. ISSN 0017-5749 (2000) [Refereed Article]

DOI: doi:10.1136/gut.47.5.622

Abstract

Introduction - Epidermal growth factor (EGF) is normally present as EGF1-53. A variety of C terminal truncated forms have been used in preliminary trials for treating gastrointestinal injury but their relative potency and stability when used in a clinical setting are unclear. Therefore, we compared the biological activity of recombinant EGF1-53, EGF1-52, EGF1-51, and the C terminal peptides EGF44-53 and EGF49-53. Methods - Purity of forms was confirmed by mass spectrometry. Bioactivity of the different EGF forms was determined using [methyl-3H] thymidine incorporation into primary rat hepatocytes and their ability to reduce indomethacin (20 mg/kg subcutaneously)/restraint induced gastric injury in rats. Stability of EGF peptides was determined by serial sampling from a syringe driver system containing: EGF/4% albumin in saline. Results - Biological activity assays of EGF1-53, EGF1-52, and EGF1-51 gave almost identical thymidine uptake dose-response curves (maximal responses increasing baseline uptake from 4400 (600) cpm (mean (SEM)) to about 22 000 (2000) cpm when EGF was added at 1.6 nM). EGF44-53 and EGF49-53 did not stimulate 3H thymidine uptake. Control rats had 47 (4) mm2 damage/stomach, EGF1-51, EGF1-52, and EGF1-53 at 0.16 and 0.80 nmol/kg/h each reduced gastric injury by about 50% and 80%, respectively (both doses p<0.01 compared with control but no significant difference between the different forms). EGF was stable at room temperature for seven days but biological activity decreased by 35% and 40% at two and three weeks, respectively (both p<0.01). Exposure to light did not affect bioactivity. Conclusion - EGF1-51 and EGF1-52 are as biologically active as full length EGF1-53 but the C terminal penta- and decapeptides are ineffective. Clinical trials of EGF can probably use infusion systems for at least 48 hours at room temperature and with exposure to light, without reducing biological efficacy.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Gastroenterology and Hepatology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
ID Code:72884
Year Published:2000
Web of Science® Times Cited:27
Deposited By:Research Division
Deposited On:2011-09-02
Last Modified:2011-09-05
Downloads:0

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