Computational and phage display screening platform for heparan sulfate peptide binders

Overview

This solution offers a discovery platform for identifying short peptide binders targeting heparan sulfate (HS), a negatively charged sugar chain found on cell surfaces that plays important roles in cell signaling, viral entry, and tumor biology. The platform combines two complementary screening strategies: computational molecular docking of virtual peptide libraries and biological phage display screening. Peptide binders identified through both routes are synthesized, fluorescently labeled, and evaluated for binding affinity using biophysical and cell-based assays.

The offering is relevant to pharmaceutical and biotechnology partners seeking targeted drug delivery vehicles, inhibitors of HS-mediated pathogen infection, or modulators of tumor-microenvironment interactions. Peptide-based HS binders offer advantages over larger biologics such as antibodies, including lower cost, easier synthesis, and improved tissue penetration.

Technical specifications

Dual screening workflow:

• Computational generation of a virtual peptide library enriched in lysine and arginine residues, designed to exploit the negative charge of HS, with the flexibility to include non-natural and non-proteinogenic amino acids
• High-throughput molecular docking of peptide candidates against HS to shortlist top 20 sequences
• Phage display biopanning against HS to independently identify biological peptide binders
• Synthesis and fluorescent labeling of top peptide hits
• Fluorescence titration assays to quantify binding affinity, with submicromolar sensitivity demonstrated in prior related work
• Cell biology validation using HS-expressing cell lines (e.g., CT26), with and without heparanase treatment to confirm HS-dependent binding

Team expertise:

• Demonstrated track record in phage display identification of 50+ peptide binders against a cellular receptor protein, with five synthesized and validated by fluorescence microscopy and FACS
• Experience in computational model building, docking, and molecular dynamics simulations through collaboration with the National Centre for Biological Sciences, Bangalore

Technology readiness level

The platform is currently at an early-to-mid stage of development (TRL 3–4). Prior work has validated the individual components — phage display screening, computational docking, and biophysical binding assays — on related targets, but no HS-specific binding data has been generated yet. The proposed 24-month validation plan progresses from initial screening (months 0–6), to peptide synthesis and labeling (months 6–12), to quantitative affinity measurement and cell-based validation (months 12–24).