BPS 2016
A Peptide Engineering Platform for Generating Stapled Long-acting Peptide Hormones
Weijun Shen
Principal Investigator, California Institute for Biomedical Research
ABSTRACT
As a drug class, peptides offer exquisite specificity and potency, but also present challenges associated with poor stability and short half-life, manifesting in the need for frequent injections, poor patient compliance, and overall compromised efficacy. Exendin-4, a glucagon-like peptide-1 receptor agonist administered twice daily via subcutaneous injection, improves glycemic control, often with associated weight reduction. To further improve the therapeutic efficacy of exendin-4, we have developed a novel peptide engineering strategy that incorporates a serum protein binding motif onto a covalent side-chain staple and applied to the peptide to enhance its helicity and as a consequence, its potency and serum half-life. We demonstrated that one of the resulting peptides, E6, has significantly improved half-life and glucose tolerance in an oral glucose tolerance test (OGTT) in rodents. Chronic treatment of E6 significantly decreased body weight and fasting blood glucose, improved lipid metabolism and also reduced hepatic steatosis in DIO mice. Moreover, the high potency of E6 allowed us to administer this peptide using a novel microstructure-based transdermal delivery system. Pharmacokinetic and pharmacodynamic studies in guinea pigs showed that a single 5 min application of a microstructure system containing E6 significantly improved glucose tolerance for 96 hours. This delivery strategy may offer an effective and patient-friendly alternative to currently marketed GLP-1 injectables. Current progress in applying this half-life extension strategy to other peptide hormones will also be discussed. References: Peng-Yu Yang, Huafei Zou, Elizabeth Chao, Lance Sherwood, Vanessa Nunez, Michael Keeney, Esi Ghartey-Tagoe, Zhongli Ding, Herlinda Quirino, Xiaozhou Luo, Gus Welzel, Guohua Chen, Parminder Singh, Ashley K. Woods*, Peter G. Schultza* and Weijun Shen* Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery, Proc Natl Acad Sci USA 2016, Early EditionAvinash Muppidi, Huafei Zou, Elizabeth Chao, Pengyu Yang, Lance Sherwood, Vanessa Nunez, Ashley Woods, Peter G Schultz*, Qing Lin* , Weijun Shen* “Design of potent, proteolytically stable oxyntomodulin analogs†ACS Chem Biol 2016,11(2):324-8
BIO
Information for BPS Presenters
The Boulder Peptide Foundation was established to further the science and knowledge of peptide technology to develop novel therapeutics, biomaterials, medical diagnostics and other beneficial uses for mankind. As part of this goal we run several programs to support career advancement, seminars and educational events. Join us on our mission to expand the applications of peptide science.
Information for BPS Presenters
The purpose of the Boulder Peptide Symposium is to encourage sharing of information related to peptide therapeutic development with an emphasis on the technical, scientific and regulatory aspects of the pharmaceutical development. Presentations that demonstrate original thinking or share experiences from case studies in product development shall receive priority over others.
The Boulder Peptide Symposium offers multiple opportunities for participants to present.
Oral Presentations in Scientific Sessions
The session topics for Scientific Program are Peptides in the Clinic, Drug Delivery, Chemistry of Complex Peptides, Spotlight on Discovery, and Peptide Showcase. Abstracts may be submitted via the Apply to Present page on the website. Submissions will be reviewed by the Scientific Advisory Board on a monthly basis and the speaker will be notified of a decision.
Presentation length: Format is 25-30 minutes slide presentation with 5-10 minutes for Q&A, with the exception of Peptide Showcase talks which are 10 minute slide presentations with 5 minutes for Q&A. Please confirm with your session chair to confirm the exact presentation length.
Invited Speakers: Speakers are requested to supply their presentation details 30 days after receiving an invitation to present.
Program Book Deadline: Final abstract and title must be provided no later than September 1st. No changes to the program are possible after this date.
Presentation Format: Oral presenters please provide your presentation slides to the A/V table on the day of your presentation.
Lodging: All speakers are requested to reserve their own room. Discount rates at the conference hotel are available until August 16th.
Registration: All speakers, excluding sponsored presentation speakers, receive a complimentary registration upon approval of the abstract.
Peptide Showcase Description
The Peptide Showcase is an opportunity for an individual or company to “showcase” new ideas, technology and pipeline assets. Priority shall be given to presentations from biotech and startup companies. Service providers and vendors are not eligible. Speakers in the session receive a complimentary event registration.
Posters
Posters can be presented on any topic relevant to peptides including original research, innovative products and technologies.
Eligibility- Any attendee (from academia, industry, biotech or vendor/sponsor) can present a poster. The presentation must contain original scientific thinking. To submit a poster go to the Submit a Poster link from the meeting menu. All submissions are reviewed on a rolling basis and will be notified of approval. September 1st is the last day to submit a poster abstract. Approved posters are published on the BPF website.
A 30 ” x 40″ board shall be provided with thumb tacks. Board will be on an easel and can be rotated for either landscape or portrait formats. Once you apply for a poster, you will get email confirmation that your poster was accepted. The poster session and number assignments will be emailed one week before the Symposium.
Poster boards shall be available for display from 8am to 8pm the day of your assigned poster session. See the program agenda for the poster session schedule.
Public Release
Every presentation at the Boulder Peptide Symposium is automatically recorded. Speakers are required to give consent for sharing of the presentation video with the peptide community.