Projects / Drug Design / Nucleotide Modifications
Case Study: CADD applied on aimed modifications of small molecules

Rational Design and Optimization of 6-thio-GTP Analogs

This project focused on the RAC1 GTPase, a key signaling protein. The goal was to develop modified nucleotides with high specificity and improved clinical profiles through multiple cycles of modeling and synthesis.

The Development Process

Structural Analysis:

  • Detailed evaluation of the RAC1-nucleotide complex to identify key interaction residues in the binding pocket.

Rational Modification:

  • Suggesting specific chemical alterations to the 6-thio-GTP scaffold to enhance hydrogen bonding or hydrophobic fit.

Iterative Re-modeling:

  • After initial synthesis and testing, the experimental results were used to re-evaluate the complex models, leading to a refined strategy for the next generation of compounds.

Clinical Profiling:

  • Assessment of metabolism and bioavailability to transform a laboratory hit into a viable drug candidate.