Cyclic amino acid linkers stabilizing key loops of brain derived neurotrophic factor

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Abstract

Based on β-turn-like BDNF loops 2 and 4, involved in receptor interaction, cyclic peptide replicas were designed, synthesized and tested. In addition to the native turn residues, the cyclic peptides include a linker unit between the N- and C-termini, selected by molecular modeling among various non-proteinogenic cyclic amino acids. NMR conformational studies showed that most of the cyclic peptides were able to adopt turn-like structures. Several of the analogues displayed significant inhibition of the BDNF-induced TrkB receptor phosphorylation, and hence could be useful templates for developing improved antagonists for this receptor.

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Acknowledgments

This work was supported by the Spanish Ministry of Education and Science (SAF 2009-09323 & CTQ2008-00080/BQU). J.L.B. was a predoctoral FPI fellow.

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