Macrocyclic peptides – unlocking the power of macrocycles
In modern drug discovery macrocyclic peptides are breaking boundaries. Since the inception of RG Discovery, we have had a strong focus on peptide chemistry in drug discovery and development settings. With its expanding role in modern drug discovery and the field of macrocycle molecular innovation our peptide chemistry and profiling services are increasingly demanded for client projects. Our deep-rooted expertise in the synthesis, profiling and analysis of complex peptides – both linear and cyclic – enables us to effectively design and develop bioactive peptide and macrocyclic molecules showing adequate stability and other desired properties. Recently we added determination experimental polar surface area (EPSA) by supercritical fluid chromatography (SFC) to our already strong in vitro physicochemical and ADME platform further enhancing our design capabilities.
Macrocycles are increasingly recognized for their unique ability to modulate challenging biological targets, including protein-protein interactions and intracellular pathways. We are dedicated to pushing the boundaries of what is possible in this space. By leveraging years of combined chemistry experience and exploiting our capabilities regarding analytical and structural profiling we can create innovative macrocyclic molecules for various therapeutic applications using a broad arsenal of cyclization techniques.
Peptide Macrocycle Chemistry – Emerging new opportunities
RG Discovery has a passion for peptide chemistry and the possibilities that macrocycles bring to the field to overcome past hurdles like bioavailability, stability and specificity, offering new avenues for targeting previously undruggable proteins. We specialize in the design, chemical synthesis, and structural characterization of both natural product-inspired and de novo macrocyclic peptides. From head-to-tail cyclization to side-chain-to-side-chain linkages, thioether bridges, and stapled peptides, we employ a diverse range of cyclization strategies tailored to meet your research goals.
Whether your needs are for conformationally constrained peptide leads, protease-resistant scaffolds, or ligands with enhanced oral absorption and/or cell permeability, RG Discovery has the know-how and infrastructure to deliver. Our chemists, computational scientists and structural biologists work together to ensure that our macrocycle designs are synthetically robust and optimized for pharmacological activity.
Small Molecule Macrocycles – Expanding the Toolbox
We also develop and synthesize small-molecule macrocycles as exemplified by development of novel kinase inhibitors. These small macrocyclic compounds are crafted by our Custom Synthesis team with the same meticulous attention to chemical detail and biological utility as our peptide-based counterparts.
Our integrated approach to small molecule macrocycles benefits from cross-disciplinary insights gained through our long experience of integrated drug discovery, resulting in novel scaffolds with drug-like properties and target-specific activity.
Advanced Analytical and Profiling Capabilities
Understanding the structure and behavior of macrocycles is essential to their success in any application. At RG Discovery, we offer full analytical support at expert level, including high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy allowing for various studies ranging from basic quality control (purity, peptide sequencing, quantification) to in-depth structural studies. We are also experienced in handling complex analytical challenges posed by constrained peptides and non-canonical amino acid incorporation. We routinely also offer in vitro characterization of physicochemical and ADME characterization of peptides and macrocycles including, but not limited to, solubility, metabolic stability, plasma stability, chromLogD and EPSA.
Our in-house NMR facility plays a crucial role in structure elucidation, allowing us to explore and determine 3D conformation and structural dynamics. A key area for NMR studies is the identification of by-products and impurities. Here, we have established methods and workflows available including quantification of small molecule impurities in peptide and protein samples down to 10 ppm.
Why Choose RG Discovery?
With a proven track record in drug discovery and peptide chemistry, RG Discovery is your trusted partner for innovative peptide, small molecule and macrocycle research. Whether you’re seeking contract research support, collaboration opportunities, or access to unique chemical space, we bring the expertise, technology, and passion required to drive your project to success.
Let RG Discovery help you harness the full potential of macrocycles – from concept to development of candidate molecule.