Meet us at the Webinar on Chemical Synthesis of Glycosylated Peptides and Proteins Improves Drug Properties
Bioactive peptides have high biological activity, but generally have low stability in plasma, are sensitive to proteases, and can be cleared from the circulation in minutes. Glycosylation is often required for optimal biologic bioactivity, especially for protein therapeutics. Selective glycosylation has the potential to improve drug potency through such effects as enhanced receptor selectivity or prolonged half-life. For example, Amgen’s Aranesp® has a three-fold longer half-life than its Epogen®, since it has 5 N-linked oligosaccharide chains compared to 3 for Epogen, permitting less frequent, more convenient dosing. Conventional mammalion, CHO-based cell culture is typically utilized to manufacture biologics that require glycosylation, but it yields heterogeneously-glycosylated species and is complex and expensive. Chemical synthesis of proteins, such as via solid-phase or solution-phase synthesis, can be used to manufacture non-glycosylated peptides and other small proteins, but has been unable to generate glycosylated peptides and proteins.
The presentation will demonstrate that optimizing glycosylated peptides’ and proteins’ physicochemical properties by a fully-synthetic manufacturing route is possible and that these optimized molecules can possess improved biologic activity. This technology for chemically synthesizing glycosylated peptides and proteins could be widely applicable to generate novel drugs.
To register please click here.
Date: Wednesday, December 2, 2015
Time: 10am EST (NA) / 3pm GMT (UK) / 4pm CET (EU-Central)
Duration: 60 minutes
Featured Speaker: Michael F. Haller, Ph.D., Board Advisor, GlyTech, Inc.
Featured Lab: The Ulijn Group
Who we are
The Ulijn Group is a truly interdisciplinary and global research group focused on peptide nanotechnology. We are scientists from various professional backgrounds such as synthetic chemistry, molecular dynamics, biochemistry, pharmacology, polymer chemistry, and molecular biology, and represent 13 different nationalities and even more diverse cultures. Lead by Professor Rein Ulijn, the founding Director of the Nanoscience Initiative at the City University of New York’s Advanced Science Research Center (ASRC), and the WestCHEM Professor of Nanochemistry at the University of Strathclyde, we share his passion for designing complex, innovative systems from simple amino acid building blocks. Peptide chemistry allows design of robust platforms that are tunable and responsive in morphology and functionality. We hope to incorporate these biocompatible and environment friendly systems to modern technology in discovering new materials for light harvesting, drug delivery, in vivo imaging, food and cosmetic ingredients, stem cell research, enzyme mimicking catalysis, and more.
Our core research can be categorized into four areas: peptide nanotechnology, biocatalytic self-assembly, enzyme responsive materials, and adaptive systems. Below, we describe two examples of specific projects that hold much potential for the discovery and application of peptide self-assembly and nanotechnology. Looking ahead, we aim to continue integrating our work into real world applications and industries in food, cosmetics, and biomedicine.Â
Group photo: The Ulijn Group self-assembled under the CUNY ASRC terrace in the autumn breeze.
Discovery of Catalytic Peptides via Biocatalytic Self-Assembly
Efficient and effective catalysis is key to biological processes/chemical reactions and while nature has evolved impressive catalysts, they have severe drawbacks of complexity and limited stability. On the other hand, the design and discovery of efficient synthetic catalysts has been limited, questioning whether this reductionist approach can be utilized for designing catalysts. We use a combined methodology for the selection of catalytic peptides utilizing phage display and self-assembling gelators.1 This new combinatorial technology allows for discovery of selective catalytic peptides for the acceleration of slow chemical reactions based on catalytic activity directly. Seven peptides, consisting of twelve amino acids each, were identified and all were shown to possess the ability to hydrolyze amide and ester bonds under physiological conditions. Although catalytic activities observed are low, an insight into the relevance towards catalyst design can be provided by these minimalistic structures. The peptides identified in this study have the tendency to behave as small molecule catalysts rather than an enzyme since binding does not play a role.
Figure 1: A. Catalytic gelation in discovery of catalytic peptides via phage display B. Peptide sequences selected by catalytic self-assembly combined with phage display. C. Turnover data for hydrolysis of p-nitrophenyl acetate by free peptides (based on a 10 minute time course).
Designer Peptide Nanostructures
Peptide self-assembly has always been an area that chemists have understood, but most of the important peptides have been found by serendipity. Molecular Dynamics is a powerful tool that can help predict the self-assembling nature of peptides while reducing the timescale to experimentally examine the properties. We implement coarse grain molecular dynamics on tripeptide systems to identify the aggregation propensity of the tripeptides.2 Using this prediction, experimental methods can be carried out on the most promising candidates to validate these nanostructures. Introduction of organic solvents has shown exciting observations where the prediction of stable emulsifiers can be achieved. We see sequence dependence for these tripeptides, which promote two classes of emulsifiers; traditional surfactant-like assemblies and interfacial nanofibrous networks, in which the latter allows for the formation of more robust and tunable emulsions.3
Figure 2: Schematic of tripeptide emulsion stabilisation A) Cartoon of the sequence dependence of the tripeptides B) FTIR of the Emulsion state C) Fluorescence microscopy of Emulsion stained with Sudan II D) Fluorescence microscope of fibrous assembly stained with Thioflavin T
References:
[1] K. Duncan et al., J. Am. Chem. Soc., 2014, 136, 15893.
[2] Frederix, P. W. et al Nat. Chem. 2014, 30. 30-37
[3] Scott, G. G. et al, Adv. Mat., 2015, accepted manuscript
The ISO 13485 Standard
Article by Adrienne Blevins Mendoza, American Peptide Company (A member of the Bachem Group)
The ISO 13485 Standard is a gold standard for Quality Management that is designed and tailored to meet the strict quality program demands manufacturers and suppliers of the Medical Device industry. ISO 13485 certification must be issued by an independent, accredited certification body that guarantees that the quality management system has been implemented, documented, used, maintained and improved by the organization in accordance with the specific ISO standard.
Key Benefits of ISO 13485 certification:
- Assurance that provided services and products must meet a high quality standard
- Increased operational effectiveness through standardized procedures
- Reduced production loss caused by failures in quality
- Reduced operational costs by increased process efficiency and reliability
- Increased customers’ trust in the organization as a safe supplier and a user of well accepted standards
The process for achieving ISO certification can be arduous, expensive, and time-consuming, and many organizations cannot complete the process. Organizations must perform a self-assessment and correct gaps to comply to ISO standards. The organization must provide examples and case-studies of how the organization has successfully implemented and benefited from the quality programs under the ISO Standards. Â After the self-assessment is complete, organizations must undergo a thorough evaluation of the quality program by an independent, accredited certification body. Any departures from the ISO Standards are not accepted, and must be resolved, and the correction must be demonstrated before certification can be issued.
Once the organization successfully achieves certification, it is continuously monitored through periodic surveillance and recertification audits that assess whether the organization continues to meet the ISO Standards. The organization must formally respond to any observations made during the audits, and these corrective actions are verified in subsequent audits by the certification body.
The Vista site celebrated their achievement in obtaining ISO 13485 certification in 2014 after overhauling the Quality Management System in order to comply with the high quality standards of the Medical Device Industry. ISO 13485 was chosen for its applicability to many of the site’s customers requiring Peptide for use in medical devices, and requiring that supplier quality programs are compliant to their own quality system requirements. The Vista site selected the world renowned and highly respected British Standards Institute (BSI) as the independent organization for certification, and can proudly display the BSI Assurance Mark.
MEET BACHEM: Loubna Kerkeb
What is your official job title at Bachem?
Director, Research Sales
How long have you been with Bachem? Where did you work before Bachem?
I have been working at Bachem Americas for 9 Years. I started as a Quality Control Scientist and have been in Sales Management since 2010. Prior to joining Bachem, I worked as a Postdoctoral researcher at the department of Biology, at the University of South Carolina
Briefly, what do you do at Bachem?
I manage the Inside Sales team. We are responsible for all sales activities as well as customer service and support for catalog and custom synthesis products in the US, Canada and Latin America.
What is your academic background/degrees or training?
I have a Ph.D. in Biology
What do you like to do outside of work (interests, hobbies)?
I enjoy reading, hiking, swimming and playing tennis.
How is the Marketing & Sales team partnering with their customers?
We try to understand the customer business needs and objectives, and offer tailored solutions. As an example, we offer support to our clients in terms of sequence design and selection of the appropriate product specifications depending on the intended use of the peptide.
What do you like most about your job?
Every customer project is an opportunity to explore and learn new things. In addition, I have the chance to work in close collaboration with colleagues across all functional areas.
What is your preferred peptide?
The antimicrobial peptide Defensin HNP-1 (human).
Thank you very much Loubna.
PEPTIDE HIGHLIGHTS
Interesting news about peptides in basic research and pharmaceutical development:
Organometallics add aryl groups to proteins selectively-Chemical & Engineering News
EM Imaging Licenses Fluorescence Imaging Agent for Early Detection of Bowel Cancer-Photonics.com
LITERATURE CITATIONS
Bachem peptides and biochemicals are widely cited in research publications. Congratulations to all our customers with recent publications!
Gonzalez-Burgos, G., Miyamae, T., Pafundo, D. E., Yoshino, H., Rotaru, D. C., Hoftman, G., Datta, D., Zhang, Y., Hammond, M., Sampson, A. R., Fish, K. N., Bard Ermentrout, G. and Lewis, D. A.
Functional Maturation of GABA Synapses During Postnatal Development of the Monkey Dorsolateral Prefrontal Cortex.
Cereb. Cortex 25, 4076-4093 (2015)
Kim, W., Zekas, E., Lodge, R., Susan-Resiga, D., Marcinkiewicz, E., Essalmani, R., Mihara, K., Ramachandran, R., Asahchop, E., Gelman, B., Cohen, E. A., Power, C., Hollenberg, M. D. and Seidah, N. G.
Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder.
Mol. Cell. Biol. 35, 3684-3700 (2015)
Hou, C. W., Mohanan, V., Zachara, N. E. and Grimes, C. L.
Identification and biological consequences of the O-GlcNAc modification of the human innate immune receptor, Nod2.
Glycobiology (2015)
Wu, L., Oshima, T., Shan, J., Sei, H., Tomita, T., Ohda, Y., Fukui, H., Watari, J. and Miwa, H.
PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASIC sensitization in human esophageal epithelial cells.
Am J Physiol Gastrointest Liver Physiol 309, G695-702 (2015)
Alhadeff, A. L., Golub, D., Hayes, M. R. and Grill, H. J.
Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor.
Am J Physiol Endocrinol Metab 309, E759-766 (2015)