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

AuthorsBaeza, J. L. ; García de la Torre, Beatriz; Santiveri, Clara M.; Almeida, R.D.; García-López, M. Teresa ; Gerona-Navarro, G.; Jaffrey, S.R.; Jiménez, M. Angeles ; Andreu, David; González-Muñiz, Rosario ; Martín-Martínez, Mercedes
Issue Date2012
PublisherPergamon Press
CitationBioorganic and Medicinal Chemistry Letters 22: 444- 448 (2012)
AbstractBased 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. © 2011 Elsevier Ltd. All rights reserved.
Identifiersdoi: 10.1016/j.bmcl.2011.10.107
issn: 0960-894X
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