Design of a conformationally defined and proteolytically stable circular mimetic of brain-derived neurotrophic factor

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of neurotrophic factors. BDNF has long been recognized to have potential for the treatment of a variety of human neurodegenerative diseases. However, clinical trials with recombinant BDNF have yet to yield success, leading to the suggestion that alternative means of harnessing BDNF actions for therapeutic use may be required. Here we describe an approach to create low molecular weight peptides that, like BDNF, promote neuronal survival. The peptides were designed to mimic a cationic tripeptide sequence in loop 4 of BDNF shown in previous studies to contribute to the binding of BDNF to the common neurotrophin rece..