Parallel synthesis and screening of peptide conjugates

Area of Science:

• Bioconjugation Chemistry
• Therapeutic Development
• Drug Discovery

Background:

• Peptide conjugates are promising therapeutics but their development is inefficient.
• Current methods for peptide conjugate discovery are low-throughput and resource-intensive.
• Optimization relies on expert knowledge rather than high-throughput screening.

Purpose of the Study:

• To develop a parallel synthesis and screening strategy for peptide conjugates.
• To improve the efficiency and throughput of peptide conjugate discovery and optimization.
• To demonstrate the strategy's utility in optimizing a clinical-stage peptide-antibody conjugate.

Main Methods:

• Utilized copper-free click chemistry for chemoselective ligation in conjugation and purification.
• Developed a method for rapid, quantitative measurement of conversion in crude conjugation mixtures.
• Implemented a purification step using an immobilized chemical scavenger.
• Employed robust analytical methods for end-product characterization.

Main Results:

• Significantly improved productivity in the generation and screening of peptide conjugates.
• Reduced variability in conjugation steps through a standardized parallel synthesis approach.
• Successfully optimized the anti-Angiopoietin-2 (Ang2) peptide-antibody scaffold conjugate, CVX-060.
• Demonstrated the effectiveness of the purification and analytical methods for complex conjugates.

Conclusions:

• The presented strategy streamlines peptide conjugate development, accelerating the discovery and optimization process.
• This approach enhances the efficiency of creating and screening peptide conjugates for therapeutic applications.
• The optimized CVX-060 conjugate, developed using this strategy, has advanced to clinical trials for oncology indications.