Optimizing novel peptides into effective and safe therapeutics
At IRBM, we harness world-class expertise in the development of peptide therapeutics and have a proven track record in the clinic. Our team has extensive knowledge in peptide and macrocyclic drug discovery in various therapeutic areas, including antivirals, oncology, cardiovascular and metabolic diseases. We have developed multiple drug candidates, including macrocycles incorporating multiple constraints, and peptides conjugated to fatty acids, cholesterol and polymers. Our expertise stems from the previous status as “Peptide Center of Excellence” at Merck Research Laboratories.
Peptide Drug Development
Our workflow for peptide drug development starts with extensive design and engineering for the optimization of multiple parameters. Our integrated platform team employs advanced synthetic strategies, high throughput screening, computer-aided drug design, phage display and NMR structural studies to optimize activity, efficacy and selectivity. We improve pharmacokinetic profiles to overcome rapid metabolism and disposition due to enzymatic degradation and renal filtration. Our team employs mass spectrometry to identify peptide metabolites from both in vitro and in vivo samples. We also screen for potential pseudo-allergic reactions caused by mast cell activation and consequent histamine release.
The workflow for the design and engineering of peptide and macrocyclic drugs includes:
- Multi-parametric optimization for activity, efficacy and selectivity
- Optimization of ADME properties
- Identification of labile hot spots
- Aggregation/oligomerization studies
- Study for pseudo-allergic reactions due to mast cell activation and histamine release
- Immunogenicity assessment
In the discovery phase, extensive expertise in chemo-selective conjugation approaches, and in solution and solid-phase chemistry, are key for the successful optimization of candidates.
The chemical approaches for peptide and macrocyclic drug optimization we employ include:
- Extensive expertise in solution and solid-phase chemistry
- Multi-analog synthesis
- Wide in-house collection of non-natural amino acids
- Ad hoc synthesis of novel amino acids and building blocks
- Backbone modification and cyclization chemistries
- Conjugation approaches
Advanced Synthetic Strategies
Our team is eager to support basic research studies and target validation. We provide peptide tools such as long and difficult peptide sequences, small proteins, labeled peptides, complex peptides and proteins with post translational modifications.
Advanced synthetic approaches employed at IRBM include:
- Microwave-assisted solid phase assembly
- Pseudo-proline chemistry
- Native Chemical Ligation
- Conjugation chemistries