title: Cyclic amino acid linkers stabilizing key loops of brain derived neurotrophic factor.
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.
authors: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, Madrid 28006, Spain.
authors: José Luis
authors: JL
authors: Baeza
authors: Beatriz G
authors: BG
authors: de la Torre
authors: Clara M
authors: CM
authors: Santiveri
authors: Ramiro D
authors: RD
authors: Almeida
authors: M Teresa
authors: MT
authors: García-López
authors: Guillermo
authors: G
authors: Gerona-Navarro
authors: Samie R
authors: SR
authors: Jaffrey
authors: M Ángeles
authors: MÁ
authors: Jiménez
authors: David
authors: D
authors: Andreu
authors: Rosario
authors: R
authors: González-Muñiz
authors: Mercedes
authors: M
authors: Martín-Martínez
mesh_terms: D000598:Amino Acids, Cyclic / Q000737:chemistry*; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry; D010766:Phosphorylation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020813:Receptor, trkB / Q000737:chemistry*; D013696:Temperature
chemical_list: D000598:Amino Acids, Cyclic; D019208:Brain-Derived Neurotrophic Factor; D010455:Peptides; D010456:Peptides, Cyclic; D020813:Receptor, trkB