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Jul 1, 2009 (Vol. 29, No. 13)

European Overview: Firms Look for Niche in Peptide Synthesis

Unique Technology or Service Allows Companies to Stand Apart from Their Rivals

  • Fluorescent Dyes

    Cambridge Research Biochemicals (CRB) works with small companies and academic groups to help commercialize new technologies relevant to the peptides market. CRB most recently signed a partnership deal with Cyanagen, giving it access to Cyanagen’s CHROMIS family of fluorescent dyes for labeling custom peptides.

    CRB says that studies have shown the CHROMIS labels perform better than the most advanced commercial dyes, with increased brightness and performance across the 400–850 nm wavelength range. About 60 ready-to-use labels are already available, and the dyes can also be designed to display different charge values (anionic, cationic, zwitterionic, and neutral), and combine with over 40 crosslinkers and biotinylating reagents.

    CRB will play an instrumental role in the EU-funded BIOSCENT project, a European collaborative program that aims to develop new bioactive polymeric scaffolds for use in stem cell-based tissue regeneration approaches to treating cardiovascular disorders and diseases. Announced in April, the project will leverage CRB’s peptide-synthesis expertise and the development of peptide-directed antibodies to identify cell signaling factors.

    “We have established a core peptide technology team, which is working with peptide research scientists in the U.K. to look at new avenues for synthesizing complex molecules such as multiple-bridged and glycosylated peptides,” says Emily Humphrys, commercial director.

    Tapping into the expertise of academically trained peptide chemists is not as easy as it sounds, however. While the custom-peptide market is growing steadily in terms of volume and peptide complexity to meet the increased demands of new proteomics applications and antibody technologies, the number of academically trained peptide chemists is dwindling, Humphrys points out.

    “Not all peptide companies are created equal,” stresses Paul Sheppard, Ph.D., scientific development director for Enzo Life Sciences (ELS). “There are few formally trained peptide chemists left in either industry or academia today, and there is now an increasing reliance upon machines to make peptides, rather than on a human element that really understands peptide chemistry. 

    “The upshot of this is that while the number of companies offering custom peptide-synthesis services is increasing, the knowledge and expertise residing within those companies has become greatly diluted; consequently the synthetic success rate and integrity of peptides obtained from some commercial providers may not rise to meet expectations.”

    Collaborative research has proven most important to ELS. “Whereas the company’s deep involvement in an area such as the ubiquitin signaling pathways led to its inclusion in a five-year EU-funded Network of Excellence (RUBICON), its peptide-based capabilities allowed the company to share this expertise with all RUBICON  members as a core facility. Such involvement has undoubtedly proven to have been to the benefit of all involved,” adds Dr. Sheppard.

  • Broadening Focus

    Click Image To Enlarge +
    Intavis Bioanalytical Instruments’ CelluSpot™ peptide array is probed with the serum of a Borrelia-infected patient.

    Intavis Bioanalytical Instruments was established nine years ago, primarily as a manufacturer of peptide synthesizers. Intavis used its expertise in the field to establish its own custom synthesis business three years ago, and this unit has experienced double-digit growth annually, says Heinrich Gausepohl, director of development.

    “While the market for state-of-the-art automated peptide synthesizers has remained buoyant and is growing steadily, the proteomics revolution has also provided extensive opportunities for custom peptide services. Our experience in peptide chemistry meant it was an obvious step for us to add custom synthesis to our instrumentation business.”

    Intavis offers custom peptides, peptide sets, and custom peptide sets for T-cell stimulation/epitope mapping. Products are centered on the company’s CelluSpots™ technology for custom peptide arrays and ready-to-use CelluSpots kinase substrate arrays.

    CelluSpots technology was developed to address some of the drawbacks associated with SPOT technology for investigating protein-protein interactions, Dr. Gausepohl claims. “While SPOT synthesis technology is well recognized as a rapid and robust method to generate peptide libraries on membrane supports, it does have some shortcomings.

    The reusability of traditional SPOT membranes is limited, the production of duplicate peptide SPOT arrays is time-consuming and expensive, and membranes are large compared with glass microarrays slides and require large sample volumes.”

    In contrast, CelluSpots are arrays of peptide-cellulose conjugates spotted on planar surfaces as a 3-D matrix, rather than as a monomolecular layer. This essentially provides a high peptide loading and concentration. “The peptides are synthesized on modified cellulose disks that will dissolve after synthesis. The dissolved peptide-cellulose conjugates are then spotted onto coated microscope slides, and form a 3-D structure that is not dissolved in aqueous solutions,” Dr. Gausepohl explains.

    “This three-dimensional structure holds up to 500 times more peptides per area in comparison with conventional monolayer deposition, and shifts the binding equilibrium to favor low-affinity protein-protein interactions. Pushing the reaction in the bound direction is particularly important as many key protein-protein interactions are believed to be weak, or occur only transiently, and would not necessarily be detected using other approaches.”

    Intavis also believes that its CelluSpots technology has a number of other benefits compared with SPOT technology. “The CelluSpots approach displays comparable chemical properties to the original SPOT membranes and is compatible with standard microarray hybridization chambers and scanners. The method also allows numerous identical copies of the same quality to be prepared easily and cost-effectively, and requires far smaller sample volumes,” Dr. Gausepohl adds.

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