Webinars
Innovation vs Application: Maximizing Efficiency in Peptide Drug Discovery from a Chemistry Perspective
Recorded Webinar from May 16, 2019
This presentation will discuss the discovery process used in the development and selection of a Glucagon agonist, including SAR studies and the positive impacts of integrating innovative technology. Faced with limited time and resources, flexible instrumentation has been used to efficiently incorporate molecular improvements that are critical for overcoming the inherent challenges of peptide drug discovery, including optimizing physical properties and receptor selectivity.
Speakers:
William Blackwell III,
Investigator, Intarcia Therapeutics
James Cain, Ph.D.,
Global Product Manager, Gyros Protein Technologies
Challenging SPPS: Difficult sequences and side reactions
Recorded Webinar from April 4, 2019
Peptide therapeutics have seen increased interest in the last decade, making peptide synthesis a critical step in the drug discovery and development process. One of the major drawbacks in peptide synthesis is that success largely depends on the peptide sequence being synthesized, so what do you do when you have a sequence with failed couplings at certain cycles? Do you extend the coupling time? Change reagents? Do multiple couplings? Here we’ll discuss our take on these questions using fast parallel synthesis optimization of a sterically hindered model peptide, Aib-ACP (VQ-Aib-Aib-IDYING-NH2) which saw improvements from 7.8% using HCTU to 91% using COMU and increasing the reaction temperature to 75 °C with short reaction times (2 x 3 min). What if your synthesis challenges aren’t difficult couplings but side reactions? We’ll discuss strategies for minimizing their occurrence during fast SPPS.
Speaker:
Cyf Ramos-Colón, Ph.D., Senior Scientist, Gyros Protein Technologies
Polar Hinges as Functionalized Conformational Constraints in (Bi)cyclic Peptides
Redorded webinar from November 8, 2018
Speakers:
Dr Alex Hoose
Post-Doctoral Research Associate
University of Glasgow
Strategies to Increase Robustness in the Optimization and CMC Production of Peptide Therapeutics with Parallel Peptide Synthesis
Recorded Webcast from TIDES 2018 Digital Week
With the advancement of personalized medicine and newer disease targets, peptide therapeutic development has greatly expanded. Its potential to achieve increased receptor specificity and decreased toxicity satisfies efficacy and safety regulatory requirements. Technology advances in automated SPPS enable screening and CMC production of peptides with greater structural complexity allows for the design of more physiologically stable products with increased target specificity and membrane permeability. Structural modification strategies for peptide lead optimization can include cyclization, stapling, and PEGylation, which can be difficult to synthesize and purify, requiring more efficient synthesis protocols and automation to ensure reproducible and efficient manufacturability.
Here we describe the process development and parallel optimization of SPPS relating to different biologically relevant peptides. Solid-support screening, reagent screening and temperature screening are demonstrated using an automated peptide synthesizer as part of the optimization process for difficult peptides such as Aib-Enkephalin (90% optimized crude purity vs 21% crude purity) and JR 10-mer (67% optimized crude purity vs 21% crude purity). In addition, the synthesis optimization in parallel of GLP-1 related peptides and dual GLP-1/glucagon receptor agonists will be shown, testing multiple resins and coupling reagents in search of optimal crude purities that may translate into ease of purification during the manufacturing process. Finally, the fully automated synthesis, from linear, on-resin cyclization, and resin cleavage, of NYAD-1 stapled peptide will be shared.
Presenter:
James Cain, Global Product Manager, Gyros Protein Technologies
Strategies for efficient, high throughput optimization of biopolymers and mimetic compounds
Peptide, peptidomimetic and oligonucleotide therapeutics are increasingly at the forefront of drug development programs for personalized medicine, cancer therapeutics, and genetic diseases among others. This has driven the search for faster and more efficient solid phase synthesis (SPS) protocols, making method development crucial in the discovery process towards scale-up. Automated synthesizers are part of the SPS toolbox that allows simultaneous optimization and high-throughput synthesis via parallel synthesis.
In this webinar, we describe the process development and parallel optimization of SPS of different biologically relevant compounds. Solid-support screening and reagent screening are demonstrated using automated peptide synthesis as part of the optimization process for peptide nucleic acids (PNA), peptoids, and cyclic peptides. For example, parallel synthesis condition scanning for the synthesis of SK-8mer PNA analog, H-Lys-AGTGGATC-Lys-NH2, led to an increase of 27% crude purity resulting in high purity product (73% crude pure) for biological analysis. Coupling reagents, resins and reaction time combinations for increased crude purity results will be discussed for biopolymers and mimetic compounds.
Presenters:
James Cain, Global Product Manager, Gyros Protein Technologies
Cyf Ramos-Colón, Senior Scientist, Peptide Applications, Gyros Protein Technologies
Cell Penetration Profiling using the Chloroalkane Penetration Assay for Peptides, Proteins and Nucleic Acids
