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Peptide therapeutics has once again become the focus of innovative drug development. As potential therapeutics, peptides offer several advantages over small molecules (increased specificity) and antibodies (small size). However, delivery and sensitivity to serum and tissue proteases coupled with short serum half-life has remained a major therapeutic stumbling block. Cambridge Healthtech Institute’s Inaugural Peptide Therapeutics addresses recently developed technologies to overcome these issues thus allowing therapeutic peptides to fulfill their promise as a widely accepted drug class.
Thursday, January 14
1:15 pm Registration for Peptides
1:45 Chairperson’s Opening Remarks
David Craik, Ph.D., Professor, Institute for Molecular Bioscience, The University of Queensland
1:50 Peptidic Tumor Targeting Agents: On the Road from Phage Display Peptide Selections to Clinical Reagents
Kathlynn C. Brown, Ph.D., Assistant Professor, Internal Medicine, Division of Translational Research & The Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical School
Tumor-specific peptidic agents hold great promise for clinical applications in cancer diagnosis and therapy. Our goal is to discover ligands specific to receptors on the surface of cancer cells that will have a clinical impact in functional diagnosis and tumor-specific drug delivery. Towards this goal, my laboratory has employed biopanning of phage-displayed peptide libraries to isolate novel peptidic tumor-binding reagents. This approach has generated a suite of cancer targeting peptidic ligands which bind with high affinity and specificity to malignant cells while avoiding their healthy counterparts.
2:20 Phylomer Libraries as a Rich Source of Potent Peptides in Phenotypic and Target-Directed Screens
Paul M. Watt, Ph.D., Chief Scientific Officer & Vice President, Corporate Development, Phylogica Ltd.
Phylomers- a new class of peptides - can exhibit superior functional hit-rates, when compared to randomly derived peptides. A Phenotypic screen for specific blockade of the AP1 dependent signaling pathway in mammalian cells will be described. Phylomer peptides have also been identified via a direct screen for binding to live bacteria, which show with potent antimicrobial activity against clinical isolates of multi-drug resistant microorganisms. Data will be presented from and in vivo studies of potent blockers of the extracellular target
2:50 Immunotherapy Using Li-Key Modified Peptides for Increased, Antigen-Specific T Helper Cell Activation
Eric von Hofe, Ph.D., President, Research and Development, Antigen Express
Peptide immunotherapeutics hold promise for cancer and other diseases, but suffer from lack of potency. In particular, the binding of epitope peptides to MHC class II molecules, necessary for activation of CD4+ T helper cells, is inherently less efficient than the binding of peptides to MHC class I molecules and activation of cytotoxic T lymphocytes. To overcome this, MHC class II epitope peptides have been modified with a fragment of the MHC class II-associated invariant chain, termed Ii-Key, to dramatically improve antigen-specific activation of T helper cells.
3:20 Evoluttion of a Protein Scaffold
GaryWoodnutt, Ph.D., Vice President of Biology, CovX Pharmaceuticals Inc.
Interest in peptide therapeutics has been revitalized by the development of protein scaffolds that improve the pharmacokinetics of these conjugates. Progressive refinement in these scaffolds and in the way the peptide is presented has further improved the properties of the overall molecule. This presentation will demonstrate the evolution of the CovX scaffold platform.
3:45 Networking Refreshment Break in the Exhibit Hall
4:30 Stapled Peptides: A New Class of Targeted Therapeutics
Vincent Guerlavais, Ph.D, Principal Scientist, Research, Aileron Therapeutics, Inc.
Stapled a-helical peptides exploit chemical stabilization of secondary structure by way of ring-closing metathesis via side-chain or backbone functionalities. By leveraging novel building blocks and macrocyclization chemistries along with sophisticated drug design, molecular informatics and biophysical analysis, Aileron’s innovative technologies are creating a molecular armamentarium of stapled a-helical peptides for a plethora of therapeutic targets.
5:00 De novo Identification of Binding Sequences for Antibody Replacement Molecules
Stephen Quirk, Ph.D., Director, Enabling Technologies, Corporate Research & Engineering, Kimberly Clark
A new in silico method has been developed that automatically identifies peptide sequences that can bind to targets of known three-dimensional structure. The method is potentially faster and more economical than traditional methods of raising antibodies by means of hybridomas or biopanning technology. The current algorithm creates a small initial peptide library and docks it to the target protein. A new library is then created based on the sequence conservation pattern deduced from the top N-scoring peptides in the first round. Successive rounds of screening, scoring, and new library creation ultimately results in the system converging to a final solution set of peptides.
5:30 De novo Sequencing of Nonribosomal Peptides
Nuno Bandeira, Ph.D., Executive Director, Center for Computational Mass Spectrometry, University of California, San Diego
While nonribosomal peptides (NRPs) are of tremendous pharmacological importance, there is currently no technology capable of high-throughput sequencing of NRPs. We propose to employ multistage mass-spectrometry (MSn) for the data acquisition, followed by alignment-based algorithms for data analysis. Since mass spectrometry based analysis of NRPs is fast and inexpensive, this approach opens the possibility of high-throughput sequencing of many unknown NRPs accumulated in large screening programs.
6:00 Close of Day
Recommended Short Courses*
Tuesday, January 12
(SC7) From Protein and Peptide Characterization to Quantitation: Advancing Mass Spec Beyond Protein Discovery
Tuesday, January 12
(SC8) Phage Display for Antibody and Peptide - Technical Tips & Guidelines
* Separate registration required