@marrugo_kelly@LatinXChem@BioMaterSci@rsc_chembio@ChemBioChem 1) Sí, la disminución de GLP-1 observada en pacientes diabéticos se refiere a su forma libre. 2) Es correcto, al estar acumulado el Cu en pacientes diabéticos, este metal podría estar coordinado al poco GLP-1 que queda en plasma y afectando su función.
@capdevilalab@LatinXChem Overall, we think that the Cu-induced interactions between PrP and Abeta could be part of mechanisms that respond to changes in metal concentration in the synaptic cleft
@capdevilalab@LatinXChem Finally, yes, we think these three ternary complexes can form in the synaptic cleft; particularly, when Cu is released after activation of NMDAR receptors. We discuss the possible physiological relevance of these species in our recently published paper https://t.co/SGjuAnCX5N
@capdevilalab@LatinXChem For the ternary complex (a-His111-Cu(II)-Abeta) named transient ternary species, we expect a Kd in microM range, similar to the ternary OR-Cu(II)-Abeta complex. Both ternary species require high Cu(II) concentrations and are not the main species when adding an Abeta excess.
@capdevilalab@LatinXChem For the other ternary complex (alpha-His111-Cu(II)-Abeta) named Mode I-like, we estimate a binding a little higher than Cu(II)-Abeta (nM range); because, in this titration, we do not detect the Cu-Abeta complex, even when adding an excess of Abeta.
@capdevilalab@LatinXChem We can make some inferences based on the affinity of Cu(II)-PrP complexes. The OR-Cu(II)-Abeta complex requires the formation of component 1 (Kd=7-10 microM), but it cannot compete with component 3 (Kd= 10 nanoM). We estimate that this ternary species has a Kd in the microM range
@capdevilalab@LatinXChem Hi! Thank you! Your questions are exciting. We detected the formation of at least three ternary complexes: one at the octarepeat region and two more with the peptide that models the alpha-cleaved His111 site. We did not determine the binding affinity of any of these complexes.