RESUMEN
Various patterns of foldameric oligomers formed by trans-ABHC ((1S,2S,3S,5S)-2-amino-6,6-dimethylbicyclo[3.3.1]heptane-3-carboxylic acid) and ß(3)-hSer residues were studied. NMR, ECD and molecular modelling demonstrated that octameric and nonameric sequences with multiple i-i+3 ABHC pair repulsions attain the ß-H18 helix in CD(3)OH. As a close relative of the α-helix, this helix type is stabilized by i-i+4 backbone H-bond interactions. The formation of the ß-H18 helix was found to be solvent- and concentration-dependent. Upon dilution, the ß-H18 â ß-H12 helix transition was revealed by concentration-dependent ECD, DOSY-NMR and TEM measurements.
Asunto(s)
Péptidos/química , Modelos Moleculares , Estructura Secundaria de ProteínaRESUMEN
Galectin-1 (Gal-1), a ubiquitous beta-galactoside-binding protein expressed by various normal and pathological tissues, has been implicated in cancer and autoimmune/inflammatory diseases in consequence of its regulatory role in adhesion, cell viability, proliferation, and angiogenesis. The functions of Gal-1 depend on its affinity for beta-galactoside-containing glycoconjugates; accordingly, the inhibition of sugar binding blocks its functions, hence promising potential therapeutic tools. The Tyr-Xxx-Tyr peptide motifs have been reported to be glycomimetic sequences, mainly on the basis of their inhibitory effect on the Gal-1-asialofetuin (ASF) interaction. However, the results regarding the efficacy of the Tyr-Xxx-Tyr motif as a glycomimetic inhibitor are still controversial. The present STD and trNOE NMR experiments reveal that the Tyr-Xxx-Tyr peptides studied do not bind to Gal-1, whereas their binding to ASF is clearly detected. (15)N,(1)H HSQC titrations with (15)N-labeled Gal-1 confirm the absence of any peptide-Gal-1 interaction. These data indicate that the Tyr-Xxx-Tyr peptides tested in this work are not glycomimetics as they interact with ASF via an unrevealed molecular linkage.
Asunto(s)
Asialoglicoproteínas/metabolismo , Galectina 1/metabolismo , Glicoproteínas/metabolismo , Péptidos/farmacología , Tirosina/química , alfa-Fetoproteínas/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Asialoglicoproteínas/antagonistas & inhibidores , Fetuínas , Galectina 1/antagonistas & inhibidores , Galectina 1/genética , Humanos , Células Jurkat , Espectroscopía de Resonancia Magnética , Péptidos/síntesis química , Péptidos/química , Unión Proteica , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , alfa-Fetoproteínas/antagonistas & inhibidoresRESUMEN
The long-range side-chain repulsion between the (1R,2R,3R,5R)-2-amino-6,6-dimethyl-bicyclo[3.1.1]-heptane-3-carboxylic acid (trans-ABHC) residues stabilize the H12 helix in beta-peptide oligomers.