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Bioorg Med Chem. 2009 Apr 1;17(7):2695-702. doi: 10.1016/j.bmc.2009.02.053. Epub 2009 Mar 4.

Modified low molecular weight cyclic peptides as mimetics of BDNF with improved potency, proteolytic stability and transmembrane passage in vitro.

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The Department of Pharmacology, The University of Melbourne, Victoria 3010, Australia.


We recently reported the development of the BDNF mimetic peptide cyclo-[dPAKKR] 1 which promotes the survival of cultured sensory neurons via a trkB independent mechanism [Fletcher, J. M.; Morton, C. M.; Zwar, R. A.; Murray, S. S.; O'Leary, P. D.; Hughes, R. A. J. Biol. Chem.2008, 283, 33375]. In the present study we prepared a series of hydrophobically-modified analogues of 1 with an eye to improving its pharmacokinetic properties. Select members of this second generation of compounds showed improved biological activity, stability in plasma, and an ability to cross model biological membranes.

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