Triazole and peptide-based molecules targeting glycosaminoglycans for drug discovery

Overview

This research program offers a mechanism-based drug design approach focused on developing triazole and small peptide-based molecules that bind to glycosaminoglycans. Glycosaminoglycans are long, sugar-chain molecules involved in many disease pathways, particularly inflammation and tumor growth. By designing ligands that selectively interact with these targets, the program aims to accelerate lead discovery for therapeutic applications in oncology and inflammatory disease.

The offering combines computational molecular modeling with experimental validation, providing partners with rationally designed molecules whose physico-chemical properties have been optimized for drug-likeness. A distinguishing feature is the ability to incorporate fluorescent tags into the designed molecules for tracking purposes, with a method to remove the tag under both laboratory and biological conditions.

Technical specifications

Design approach:

• Molecular modeling and molecular dynamics simulations based on crystal structures of glycosaminoglycans
• Mechanism-based drug design targeting inflammatory and cancerous disease pathways
• Physico-chemical property optimization, including partition coefficient (logP) and total polar surface area (TPSA)
• Molecular mass range targeted between 200 and 400 daltons

Molecule classes:

• Triazole-based small molecules
• Small peptide-based ligands
• Fluorescent-tagged variants with optional removable tag capability

Validation methods used in prior work:

• NMR, ITC, UV-vis, and fluorescence spectroscopy
• Enzyme immuno-assays
• Animal model testing for tumor growth and inflammation targets

Technology readiness level

The underlying design methodology and validation workflow have been applied to develop lead molecules against tumor growth and inflammation, with screening through physico-chemical and biological assays followed by animal model testing. For the current glycosaminoglycan-targeting project, molecular modeling studies have been performed to identify candidate binding molecules. Future validation will involve designing new ligands with optimized polarity and partition coefficient, extending the molecular mass range to 200 to 400, and incorporating the fluorescent tagging feature with removable tag capability for both in-vitro and in-vivo use.