Webinars

RECORDED WEBINARS

SPPS Tips for Success: Strategies for Minimizing Side-Reactions

Recorded Webinar from May 26, 2020

As peptide chemists strive to achieve new methods and techniques for solid phase peptide synthesis (SPPS), strategies must also be implemented to help reduce the occurrence of unwanted side reactions that inevitability take place during the chemical synthesis process. Attend this free webinar to learn how to implement preventative measures to help reduce or eliminate unwanted side products from forming.

Speaker:
Lukasz Frankiewicz PhD, Senior Product Specialist
Gyros Protein Technologies

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Venom Peptides: Rethinking Voltage-Gated Sodium Channel Inhibition

Recorded Webinar from May 22, 2020

In this webinar, delineating the mechanism of action behind venom peptide inhibition of voltage-gated sodium channels will be presented. This will include discussion on engineering peptides to achieve subtype specificity and complete inhibition of specific sodium channels to unlock the potential of potent venom peptides as therapeutic leads for the treatment of pain.

Speaker:
Christina I. Schroeder, Stadtman Investigator,
National Cancer Institute, National Institutes of Health

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SPPS Tips for Success: Designing a Synthesis

Recorded Webinar from May 5, 2020

With the increasing chemical complexity of therapeutic peptides, how can you maximize the likelihood of success when developing a solid phase synthesis protocol to automate synthesis for a new peptide sequence? View this webinar to learn how to design SPPS synthesis protocols, analyze sequences and understand which factors influence decisions such as resin selection, choice of chemistry and coupling protocol.

Speaker:
Cyf Ramos-Colon PhD
Senior Scientist
Gyros Protein Technologies

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Sequence-Specific “Peptoids” for Antifouling, Antibacterial and Self-Assembly Applications

Recorded Webinar from November 15, 2019

In this webinar, sponsored in partnership with Xtalks K.H Aron Lau will highlight recent efforts in exploring solid-phase synthesized peptoids for applications beyond their conventional use in combinatorial drug discovery. 

Speaker:
K.H Aaron Lau, PhD
Senior Lecturer (Associate Professor),
Department of Pure and Applied Chemistry,
University of Strathclyde, Glasgow, Scotland, United Kingdom

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Sustainability Considerations in Peptide Chemistry

Recorded Webinar from August 22, 2019

In this webinar, sponsored in partnership with Xtalks, Craig Jamieson will discuss current efforts in the peptide chemistry community towards pursuing more sustainable replacement solvents for peptide synthesis, as well as other considerations such as coupling chemistry.

Speaker:
Craig Jamieson, PhD
Senior Lecturer
University of Strathclyde, Glasgow, UK

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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

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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

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Polar Hinges as Functionalized Conformational Constraints in (Bi)cyclic Peptides 

Redorded webinar from November 8, 2018

Protein-protein interactions (PPI’s) mediate interactions that are not only essential to homeostasis, but are also responsible for initiating and maintaining a range of physiological disorders. As a result, the inhibition of PPI's is of increasing importance to the field of drug discovery. Despite the progress that has been made in the field of PPI modulation, the development of molecules that can interfere with protein-protein interactions remains challenging. Since contact surfaces involved in PPI’s are normally large and flat, it is a serious challenge for the traditional “small-molecule” approach to effectively disrupt such a large interface. In order to address this issue, we wish to devise larger biomolecular constructs, such as cyclic peptides and peptidomimetics as PPI inhibitors. The Liskamp group has developed 'Polar hinges’ (see 'Polar Hinges as Functionalized Conformational Constraints in (Bi)cyclic Peptides, ChemBioChem, 2017, 18 (4), 387-395') as scaffolds for the cyclization of peptides, which in turn yielded bicyclic peptides and cyclized peptides with improved solubility and biological activity. During the course of this research, we noted that aqueous solubility of candidate PPI inhibitors is an absolute prerequisite not only to be able to handle and purify our target peptides; but this intrinsic property is also crucial for validation of biological activity.

Learning Objectives:

  • Challenges in the development of molecules that interfere with protein-protein interactions (PPI inhibitors)
  • Cyclic peptides and peptidomimetics as PPI inhibitors
  • Polar hinges as scaffolds for the cyclization of peptides to yield bicyclic peptides and cyclized peptides
  • Importance of aqueous solubility of candidate PPI inhibitors in the validation of biological activity
Speakers:
Dr Alex Hoose
Post-Doctoral Research Associate
University of Glasgow


Professor Rob Liskamp

Chair of Chemical Biology and Medicinal Chemistry & Guest Professor of Molecular Medicinal Chemistry at Utrecht University
University of Glasgow & Utrecht University (The Netherlands)

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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

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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

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Cell Penetration Profiling using the Chloroalkane Penetration Assay for Peptides, Proteins and Nucleic Acids

Biotechnology promises the ability to control biology and disease with laser-like precision, but biomolecules typically have poor cell penetration and unpredictable subcellular localization. Hundreds of peptides, proteins and nucleic acids are being developed as diagnostics and therapies. For many of these, intracellular delivery remains the primary obstacle. Currently, there are no quantitative, high-throughput tools to measure how much of a biomolecule enters a cell and where it distributes within the cell. Importantly, most widely-used methods for measuring cell penetration cannot rule out effects of material at the cell surface or trapped in endosomes.
We have devised a chloroalkane penetration assay (CAPA) that exclusively measures penetration to the cytoplasm. CAPA uses a cell line with stably expressed HaloTag in the cytoplasm, and measures the extent of covalent reaction between this enzyme and a small chloroalkane tag appended to the molecule of interest.

Presenter:
Joshua Kritzer
Associate Professor
Department of Chemistry
Tufts University

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Chemical, Computational, and Instrumental Tools for Challenging Peptide Syntheses

The Kay lab at the University of Utah is focused on D-peptide inhibitor development, which requires the chemical synthesis of mirror-image protein targets. Mirror-image proteins are not found in nature and are promising therapeutic agents due to their resistance to degradation by natural proteases. This webinar will describe the use of chemical, instrumental, and computational tools to overcome challenges associated with the chemical synthesis of large proteins via Fmoc solid-phase peptide synthesis and native chemical ligation. Specific examples will include the use of a reversible solubilizing tag (“helping hand”), pseudoproline dipeptides, UV monitoring, and an automated ligator program (“Aligator”) to predict the most efficient synthesis schemes.

Speakers:
Michael S Kay MD/PhD
Professor
Biochemistry, University of Utah

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