Peptides PGP and GPGPGP were found to be stable on incubation in horse gastric juice and with hydrochloric acid and pepsin; the fact that these peptides are virtually unaffected by aggressive environmental conditions means that they can fulfill their therapeutic potential in protecting the gastric mucosa from various ulcerogenic factors, including almost all known models of ulcer formation. Studies of the interaction of PGP N-acylated with docosahexaenoic acid (DHA-PGP) with horse gastric juice showed that about 90% of this compound was split into PGP and DHA within 5 min. This fact explains why the antiulcer effects of DHA-PGP and PGP are essentially identical in published in vivo experiments using stress, while DHA-PGP was about 20% more effective than PGP in an ethanol model, where deacylation of DHA-PGP is slowed because of adsorption of DHA-PGP to the walls of gastric cells.
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The authors would like to thank Professor V. V. Bezuglov (Academician M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences) for synthesizing DHA-PGP in the quantities required for the studies reported here.
This work was partially supported by the “Molecular and Cell Biology” Basic Sciences Program of the Presidium of the Russian Academy of Sciences, the Russian Foundation for Basic Research, Scientific Schools Grant No. NSh-3626.2005.4, and Grant No. MK-2375.2009.4 from the State Young Russian Scientists Support Program.
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 44, No. 11, pp. 30 – 32, November, 2010.
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Shevchenko, K.V., Trufanova, A.V. & Nagaev, I.Y. Stability of the antiulcer peptides PGP, DHA-PGP, and GPGPGP in horse gastric juice. Pharm Chem J 44, 616–618 (2011). https://doi.org/10.1007/s11094-011-0530-1
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DOI: https://doi.org/10.1007/s11094-011-0530-1