Molecular docking studies identified a dinucleoside connected with d‐aspartic acid residue as a more suitable competitive inhibitor of ribonuclease A. The chirality carbon of the d‐aspartic acid residue imposes a curvature in the molecule which is expected to make it a better inhibitor than its l‐aspartic acid congener due to more efficient binding with the active site. Experimental data established that the rational design of a dinucleoside by incorporating the predefined chirality in the backbone of the dinucleoside resulted in a half‐fold decrease of the inhibition constant compared to that of the l‐aspartic acid modified analogue. The dinucleoside also showed better lipophilicity as well as lower toxicity and opens up a new strategy for designing new class of inhibitors for RNase A.

No abstract