Which such modifications most effectively balance cost, in vivo and intracellular mobility, stability, and most importantly, binding affinity and specificity, remain to be determined.
Among the analogues, 13c exhibited the most potent binding affinity with a Ki = 0.7 μM.
An unexpected finding from the work on Kaiso and ZFP57 is that both proteins bind methylated DNA asymmetrically, with one strand contributing most of the binding affinity.
The results indicate that although the binding specificity may be guided by molecular shape and H-bond interaction, the charge and hydrophobic interactions contributed most to the binding affinity.
Compound 18d displayed the most potent ERα binding affinity with RBA value of 2.83%, while 16d exhibited the best anti-proliferative activity against MCF-7 cells with IC50 value of 4.52 ± 2.47 μM.
MD simulations and subsequent MM GBSA calculations revealed that the hydrophobic interactions between all compounds and HSP90α contributed the most to the binding affinity and a good linear correlation was obtained between the calculated and the experimental binding free energies (R = 0.88).
These studies revealed that most of the binding affinity (∼50%) is attributed to the phosphate moiety of the pTyr residue while residues in positions from −2 to +4, relative to the phosphotyrosine, modulate binding specificity.
As hot spots contribute most to the binding affinity and strength of protein interactions, understanding hotspot residues is a fundamental problem in molecular biology [see two surveys DeLano (2002b); Moreira et al. (2007)].
Of all aforementioned inorganic ligands, chalcogenidometalates have received the greatest attention due to their (for most cases) stronger binding affinity to NC surfaces, including metals (Au, Pd) and semiconductors (CdSe, PbS, InAs, InP, etc)., leading to fast and complete exchange of the native organic capping molecules.
