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Source:

Neuroreport. 2016 Feb 25.

Abstract

The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD.

Source:

Chembiochem. 2016 Mar 2;17(5):415-20. doi: 10.1002/cbic.201500601. Epub 2016 Feb 16.

Abstract

Isotope-edited two-dimensional Fourier transform infrared spectroscopy (2 D FTIR) can potentially provide a unique probe of protein structure and dynamics. However, general methods for the site-specific incorporation of stable (13) C=(18) O labels into the polypeptide backbone of the protein molecule have not yet been established. Here we describe, as a prototype for the incorporation of specific arrays of isotope labels, the total chemical synthesis-via a key ester insulin intermediate-of 97 % enriched [(1-(13) C=(18) O)Phe(B24) ] human insulin: stable-isotope labeled at a single backbone amide carbonyl. The amino acid sequence as well as the positions of the disulfide bonds and the correctly folded structure were unambiguously confirmed by the X-ray crystal structure of the synthetic protein molecule. In vitro assays of the isotope labeled [(1-(13) C=(18) O)Phe(B24) ] human insulin showed that it had full insulin receptor binding activity. Linear and 2 D IR spectra revealed a distinct red-shifted amide I carbonyl band peak at 1595 cm(-1) resulting from the (1-(13) C=(18) O)Phe(B24) backbone label. This work illustrates the utility of chemical synthesis to enable the application of advanced physical methods for the elucidation of the molecular basis of protein function

Source:

Cell Chem Biol. 2016 Jan 21;23(1):31-44. doi: 10.1016/j.chembiol.2015.11.012.

Abstract

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large group of structurally diverse natural products. Their biological activities and unique biosynthetic pathways have sparked a growing interest in RiPPs. Furthermore, the relatively low genetic complexity associated with RiPP biosynthesis makes them excellent candidates for synthetic biology applications. This Review highlights recent developments in the understanding of the biosynthesis of several bacterial RiPP family members, the use of the RiPP biosynthetic machinery for generating novel macrocyclic peptides, and the implementation of tools designed to guide the discovery and characterization of novel RiPPs.

REGISTER NOW Preliminary Program Submit Presentation Apply for the Young Investigator Award

Notes 3/18/16 Call

Attending Dan DiOlivera (Ipsen), J Fricker, Y Angell, C Rhodes, S Reza

1. Notes from Daniel - Showcase Feedback.dox (copied below)

2. Yvonne – follow up with all panelists

3. Scientific v.s. Investment Pitches

PSE more investment oriented

(pose questions to audience. “give example of.... that changed your business plan)

More coaching for presenters on investment pitch format

Intake form could direct presenters - Investor/Entrepreneur help (Ben Littauer)

- VC/Angel websites with info on how to present

4. How to charge free / early registration / full price

(issue possible due to program formed last minute.. early registration up until program formed?)

5. How far did companies travel to Cambridge? What's the viability of an annual event?

West Coast – coupling with Peptide Therapeutics (S.F. - more invest., San Diego – Less expensive)

Microsoft NERD - 9 month reservation lead time

6. Formatting / downloaded agenda doesn't show properly

Design agenda page on website to automatically format schedule for printing

Vice President of Scientific Affairs
Ipsen

Girish Aakalu is Ipsen's Vice President of Scientific Affairs North America with responsibility for scientific partnering in US and Canada.  Prior to joining Ipsen, Girish was Executive Director and Head of Strategy, Innovation, and Operations for Pfizer’s External R&D Innovation (ERDI) team.  In this role, Girish lead several strategic initiatives including establishing R&D Innovate, Pfizer R&D's strategic investment vehicle, and the spinout of Labrys Biologics (acquired by Teva).  Girish also played a key leadership role in the Pfizer-Wyeth integration process.  Prior to joining Pfizer, Girish was part of Genentech's BioOncology Pipeline Market Planning group where he was responsible for guiding the clinical and commercial strategy for late pre-clinical and early development programs including Kadcyla, Perjeta, and Erivedge.  Girish was also part of Genentech's Business Development team.  Girish started his career at L.E.K. Consulting.  Girish earned both his PhD in Cellular and Molecular Neurobiology and his MS in Biology at the California Institute of Technology in Pasadena, CA.  He received his BA in Biophysics from the Johns Hopkins University in Baltimore, MD.  

Founder / Managing Partner
CTI Life Sciences Fund

Janelle R. Anderson is Managing Partner at CTI Life Sciences Fund and host of the biotech VC podcast, Human Proof of Concept. Prior, she was Managing Director of MRL Venture Fund, the corporate venture arm of Merck focused on innovative therapeutics. She also worked several years at Merck in biologics, vaccines, and external R&D, and various roles within Finance. Dr. Anderson had previously been at seed-stage VC firm Carrot Capital Healthcare Ventures where she built startups as Entrepreneur-in-Residence, including serving as Acting CEO of Access Scientific Inc.  She worked previously as a management consultant in the healthcare practice area at BCG.  Dr. Anderson earned a BS in chemistry from McGill University and an AM and PhD in Chemistry from Harvard University.

Angel Investor
Boston Harbor Angels and
Walnut Venture Associates

Ben Littauer is an angel investor with expertise in Internet and communications technologies, as well as healthcare IT.  Currently an active member of Boston Harbor Angels and Walnut Venture Associates with investments in a wide variety of startups, he sits on the boards of several portfolio companies. He is a mentor for Mass Challenge andThe Capital Network, and is on the advisory board at TCN. Mr. Littauer is a judge for Mass Challenge, CRDF Global, and various academic competitions.

Mr. Littauer was Technology Strategist for Beth Israel Deaconess Medical Center in Boston, where he defined the architecture for PatientSite, allowing patients to communicate securely with their healthcare team and view their own medical records.  He was a consultant to the Massachusetts Health Data Consortium on healthcare data security projects.

Mr. Littauer was co-founder, President, and CTO of Baranof Software, the leading vendor of service-level management software for messaging and Internet applications. Baranof was sold to Tally Systems in 1997.

He has worked for Cisco Systems, Sun Microsystems, Symantec, Lotus, and BBN. Mr. Littauer was also an analyst with Ferris Research and Baroudi Bloor International.

Laura Davis is an early stage investor who is interested in helping entrepreneurial life scientists translate their work from the bench to the marketplace. Her background is in the life sciences - she did her graduate training at Rockefeller University, and her postdoctoral work at the Whitehead Institute, where she was a Helen Hay Whitney Fellow and a Lucille P Markey Scholar. As a Howard Hughes Assistant Investigator at Duke University Medical School and the Rosenstiel Center at Brandeis University, she oversaw an active laboratory using molecular genetics to study intracellular trafficking, and authored numerous publications. She has taught genetics and cell biology to undergraduate, graduate and medical students, as well as to the Knight science journalism fellows at MIT. She has also served on several NIH and NSF grant review committees, and as a reviewer for well-respected scientific journals. Dr. Davis is currently a managing director of Golden Seeds, an angel investor group focusing on women-owned, women-led companies that provides early stage and growth capital across all sectors to women entrepreneurs.

Co-founder and CEO
Cyta Therapeutics, Inc.

Ms. Fendrock is a life science entrepreneur and executive. Ms. Fendrock is the CEO and Cofounder of Cyta Therapeutics, a spin-out from UMass, Amherst. Cyta is developing targeted therapeutics based on the polymeric nanogel chemistry of Professor S. “Thai” Thayumanavan. Prior to Cyta, Ms. Fendrock was CEO and Co-founder of Hepregen Corporation, a venture backed, commercial stage, MIT spin-out based on Professor Sangeeta Bhatia’s bioengineered technology. With over 25 years of experience in life sciences, Ms. Fendrock has worked in high growth, environments where efficient execution to build new businesses is at a premium. Ms. Fendrock held management roles in foundational biotechnology companies including Genzyme, Somatix (one of the first gene therapy companies), Genetics Institute and Acusphere. She worked in research and product development at Integrated Genetics and Centocor. In 2012, Ms. Fendrock was honored along with other innovation leaders as one of the Mass High Tech ‘Women to Watch’. Ms Fendrock is a Director, Executive Women Series, for the Boston Chapter of the Healthcare Businesswomen’s Association (HBA) and volunteers as a mentor to entrepreneurs. Education: B.A., Molecular Biology, Wellesley College S.M., Interdisciplinary Science, MIT M.B.A., The Wharton School, University of Pennsylvania; Management of Technology Fellow