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Tel +41 58 595 2021 Tel +1 888 422 2436 Tokyo 103-0012 - Japan
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Email sales.ch@bachem.com Fax +1 310 539 9428 Email sales.jp@bachem.com
  E-mail sales.us@bachem.com  

PEPTIDE TRENDS JULY 2020

CUSTOM SYNTHESIS AND TIDE FLUOR DYES

Although Bachem offers a large number of different research grade biologically active peptides, biochemicals, substrates and inhibitors from stock, your project may require a peptide not listed in our catalog. By choosing Bachem as your custom synthesis partner you will have access to our knowledge base of close to 50 years experience in designing and synthesizing novel peptides and related organic compounds according to customer requirements. Our peptide chemists can prepare compounds according to your specifications. We are proficient in solution phase peptide synthesis and solid phase peptide synthesis, using Fmoc or Boc chemistries. We are experts in producing fluorescently labeled peptides and other modifications. We can supply with:


• research to commercial scale quantities, from milligrams to kilograms and tons
• non-GMP to GMP quality
• short peptides to small synthetic proteins
• peptides to peptidomimetics to complex organic molecules.

 

Quality and Efficient Service

Bachem is committed to using synthesis and purification strategies that yield products of the quality and purity you require. Our standard analytical package typically includes mass spectrometric analysis and determination of purity (by RP-HPLC). Additional analytics, such as the determination of the peptide content, are offered as well. Our proficient peptide synthesis techniques in combination with high capacity and state-of-the-art production equipment allow short delivery times without compromising quality. You will get technical support from a team with a strong scientific background to design your peptides and complex organic molecules and we will identify which services suit the best your requirements.

We offer additional features, such as custom synthetic procedures, traceability and change control as well as customized vialing of your product prior to delivery. Bachem sets industry standards for high quality custom peptides.

 

Reliable Supplier

Throughout discovery, development and commercialization, Bachem is your dependable partner. Our expert staff will evaluate your project and consult closely with you to ensure that the manufacturing of your product meets your specifications. From our center of excellence for research chemicals or from one of our fully qualified GMP facilities, we are fully prepared to supply you with your custom peptide how and when you need.

Multiple facilities with overlapping capacity ensure that your vital projects are completed on schedule

 

Labeled Peptides and Amino Acids

Fluorescently labelled peptides are a powerful tool in the elucidation of biochemical processes. In order to support researchers worldwide, Bachem offers a large amount of dye labelled products as part of its catalog portfolio. Additionally, our custom synthesis service offers labeling with various dyes as a standard modification. Our dye selector is the best way to browse the comprehensive range of fluorescently labelled products at Bachem.

 

A new generation of dyes: Tide FluorTM Dyes

The requirements on fluorescent probes and quenchers are manifold and high. They should have an efficient excitation, a light absorption and a high yield of emission by the donor label (dye) as well as a good energy absorption by the acceptor (quencher). This is particularly important under physiological conditions, where often only low dye concentrations can be used. Furthermore, the dyes should have a high photo-stability, in order to minimize bleaching caused by exposure with high light intensities, used for example in microscopy.

All these features are possible with Tide FluorTM dyes and the corresponding Tide QuenchersTM, from our newest partner, AAT Bioquest, Inc. They combine the cost advantages of classic fluorescent tags with the performance of proprietary dyes, or even outperform the latter in the relevant characteristics, described below


• efficient absorption of excitation light
• from common light sources
• significantly stronger fluorescence, than most conventional or proprietary dyes
• significantly higher photo-stability, than most conventional or proprietary dyes

 

Tide QuencherTM

For optimum results in FRET analysis, the Tide FluorTM dyes should be combined with the proprietary quenchers of the Tide QuencherTM range. The emission spectra of the Tide FluorTM dyes have a great overlap with the excitation spectra of the recommended Tide QuencherTM acceptors, leading to an efficient quenching process.

Also in comparison to the majority of classic and proprietary quenchers, Tide QuencherTM labels have


• significantly higher absorption strength
• superior quenching efficiency.

Similar to Tide FluorTM dyes, Tide QuencherTM labels are available with improved water solubility.

Bachem has identified Tide FluorTM dyes and Tide QuencherTM as its fluorescent labels of choice for high performance applications. These compounds cover the whole range of visible light as well as parts of the ultraviolet and near infrared region (see Table below).

Tide Fluor™- Dye Absorption (TF) Emission ε
(M-1cm-1)*
QY** Optimum Tide Quencher™ Absorption (TQ)
Tide Fluor™ 1 345 nm 442 nm 20,000 0.95 Tide Quencher™ 1 ~490 nm
Tide Fluor™ 2
Tide Fluor™ 2 WS
500 nm
495 nm
527 nm
518 nm
75,000
75,000
0.90
0.90
Tide Quencher™ 2
Tide Quencher™ 2 WS
~520 nm
Tide Fluor™ 3
Tide Fluor™ 3 WS
555 nm
555 nm
584 nm
565 nm
78,000
150,000
0.85
0.10***
Tide Quencher™ 3
Tide Quencher™ 3 WS
~570 nm
Tide Fluor™ 4 590 nm 618 nm 90,000 0.91 Tide Quencher™ 4 WS ~610 nm
Tide Fluor™ 5 WS 649 nm 664 nm 250,000 0.25 Tide Quencher™ 5 WS ~670 nm
Tide Fluor™ 6 WS 649 nm 695 nm 220,000 0.18 Tide Quencher™ 6 WS ~704 nm
Tide Fluor™ 7 WS 749 nm 775 nm 275,000 0.12 Tide Quencher™ 7 WS ~763 nm
Tide Fluor™ 8 WS 775 nm 807 nm 250,000 0.08 - -

* Extinction coefficient, determined at λmax (absorption maximum).

** Quantum yield in aqueous buffer (pH 7.2).

*** Fluorescence intensity is significantly increased when coupled to proteins or long peptides.

 

Tide FluorTM dyes and Tide QuencherTM dye labeled peptides are available as


• carboxylic acids
• maleimido-, azido- and alkyne- derivatives
• active esters (NHS)
• amines

Bachem offers a growing number of Tide FluorTM labeled dyes from stock as part of its catalog portfolio. Furthermore, we offer the labeling of products from our catalog with Tide FluorTM dyes as part of our custom synthesis service.

 

Backbone Modifications

In addition to fluorescent dyes, Bachem offers a large selection of modifications as part of our catalog and custom synthesis service. A significant compilation is listed below


• Branched Peptides
• Cyclic Peptides
• Depsipeptides
• Hydrocarbon-Stapled Peptides
• Lipidation
• Maleimido and Clickable Peptides
• MAP Peptides
• Methylation
• Multiple Disulfide Bond Formation
• N- and C-terminal Modifications
• Non-natural Amino Acids
• Peptidomimetics
• Phosphorylation and Sulfation

For more details on Customs synthesis at Bachem, please consult our new brochure: please click here

For more details on Tide FluorTM dyes and fluorescent probes:

please click here for our website page on dyes selector

please click here for our website page on fluoroscent dyes

please click here to see our monograph on FRET substrates

FLUORESCENT PEPTIDES IN CLINICAL DEVELOPMENT - OPTICAL MEDICAL IMAGING

Fluorescently labeled peptides have the potential to make a positive impact on image-guided surgery and disease diagnosis. A technique of increasing interest involves the use of fluorescent peptide probes that bind or become modified by a molecular target overexpressed at the disease site. Some examples of fluorescently labeled peptides in the later stages of clinical stages of development for imaging applications are shown in Table 1.

Table 1: Selection of Fluorescent Peptides in Clinical Development

Product Name Companies Involved Highest Phase Applications
AVB620 Avelas Biosciences Inc. III Breast Cancer
BLZ-100 Blaze Bioscience Inc. III Pediatric Central Nervous System Tumor
EMI-137 Edinburgh Molecular Imaging, University Medical Center Groningen II Barrett Esophagus,
Esophageal Cancer,
Dysplasia in Barrett Esophagus,
Papillary Thyroid Cancer,
Lymph Node Metastases, Colon Cancer

 

AVB-620

Avelas Biosciences is focusing on the development of AVB-620, which is a cell penetrating peptide-fluorescent imaging agent designed to provide real-time cancer detection during surgery. The peptide undergoes proteolytic cleavage by matrix metalloproteinases (MMPs) that have higher activity in cancerous tissue. With cleavage, the fluorescent emission wavelength changes and fluorescent intensity increases, generating a ratiometric readout. AVB-620 is administered by intravenous infusion before surgery and imaging is performed with a near-infrared camera system to identify critical cancer margins (1). In 2018, Avelas presented initial results from the first part of a Phase II clinical trial of AVB-620 that demonstrated the potential of using AVB-620 during breast cancer surgery to identify malignant tissue and lymph nodes intraoperatively (2). The company completed a Phase II/III study of AVB-620 in the first half of 2020 and plans to announce topline data in the coming months (3). Additional cancer surgery applications for potential future exploration include ovarian, colorectal, lung, head and neck, melanoma and carcinoma.

 

BLZ-100

Blaze Bioscience is developing BLZ-100 (tozuleristide) for use as a tumor-targeting optical imaging agent during cancer surgery for a range of cancer types including brain, breast, prostate, lung, colorectal and skin cancers. BLZ-100 is used to “paint” tumors in order to guide surgeons during the removal of cancerous tissue. The tumor paint consists of chlorotoxin, a tumor penetrating peptide, conjugated to indocyanine green dye, which emits light in the near-infrared range. In April 2020, the company announced that the U.S. Food and Drug Administration granted Fast Track designation to tozuleristide for pediatric central nervous system tumors (4). Currently, BLZ-100 is being evaluated in a Phase II/III clinical study in pediatric central nervous system tumors (5).

 

EMI-137

Edinburgh Molecular Imaging, a spin-off company from the University of Edinburgh, is developing EMI-137, an imaging agent that specifically targets the biomarker c-Met. EMI-137 is a 26 amino acid cyclic peptide conjugated with a modified cyanine 5 as the fluorescent dye (6). The company completed a Phase IIb clinical trial of EMI-137 in patients with suspected colorectal cancer in November 2019 (7). In addition to imaging colorectal cancer, EMI-137 is also being testing for other applications such as the diagnosis of cancers or for surgical margin delineation in breast, head, neck, and ovarian cancer.

 

Conclusion

Fluorescently labeled peptides are valuable tools for molecular imaging and over the past decade, more fluorescent peptide probes have been entering clinical trials. To support the development of labeled peptides for research and clinical applications, Bachem provides a one-stop shop for the custom synthesis of labeled peptides and amino acids. For custom synthesis, please contact our Custom Synthesis team to request a quote for your labeled peptide or amino acid.

 

References

1) S.L. Chen et al. Abstract P2-14-07: Use of an activatable cell penetrating peptide-fluorescent imaging agent (AVB-620) to identify positive and close margins intraoperatively, Cancer Research 79(4), P2-14-07 (2019)

2) Avelas Biosciences presents Phase II, Period 1 data in poster session at San Antonio Breast Cancer Symposium, Avelas Biosciences (2018)

3) Avelas and Axelarx announce collaboration to accelerate the development of promising nerve imaging agents, Avelas Biosciences (2020)

4) Blaze Bioscience announces FDA has granted Fast Track designation to BLZ-100, Blaze Bioscience (2020)

5) Study of tozuleristide and the Canvas Imaging System in pediatric subjects with CNS tumors undergoing surgery, ClinicalTrials.gov (2019)

6) S.A Esfahani et al. Optical imaging of mesenchymal epithelial transition factor (met) for enhanced detection and characterization of primary and metastatic hepatic tumors. Theranostics 6(12), 2028-2038 (2016)

7) Edinburgh Molecular Imaging commences Phase II European cancer trial, Edinburgh Molecular Imaging (2017)

MEET BACHEM, STEFANO FERRARI

PT: What is your official job title at Bachem?

Stefano: My job title is Project Manager.

 

PT: How long have you been with Bachem? Where did you work before Bachem?

Stefano: I have been with Bachem since 2007. After 12 years as team leader QC, I took over my actual position at BD & Sales last year. Before joining Bachem, I worked for a big pharmaceutical company.

 

PT: Briefly, what do you do at Bachem?

Stefano: As project leader, I have the responsibility to initiate, coordinate and supervise the tasks and goals defined for the assigned projects.

 

PT: What is your academic background/degrees or training?

Stefano: I have a MSc degree in chemistry from the University of Basel and a Ph.D. from the Swiss Federal Institute of Technology of Zurich with a strong background in analytical chemistry.

 

PT: What do you like to do outside of work?

Stefano: Besides enjoying time with my family, I like to explore our beautiful landscape by mountain bike, to play the drums at the carnival of Basel and to observe the beautiful Swiss landscape from above with small airplanes.

 

PT: What makes a perfect day for you?

Stefano: The perfect day is when the project team has successfully achieved an important project goal and additionally when I could enjoy time with my family or one of my hobbies.

 

PT: What do you like most about your job?

Stefano: I mostly like the versatility of my function, the exchange with the customers and the possibility to promote successfully the projects together with my project team colleagues.

 

PT: What is your preferred peptide?

Stefano: Due to the recently approved new pharmaceutical application forms, the corresponding benefits for the affected patients and the positive development for Bachem, my preferred peptide is Glucagon.

 

PT: Thank you very much Stefano.

LITERATURE CITATIONS

Bachem peptides and biochemicals are widely cited in research publications. Congratulations to all our customers with recent publications!

 

R.Pola et al.

Targeted polymer-based probes for fluorescence guided visualization and potential surgery of EGFR-positive head-and-heck tumors.

Pharmaceutics 12, (2020)

 

X.Zhou et al.

Environment-sensitive fluorescent inhibitors of histone deacetylase.

Bioorganic & Medicinal Chemistry Letters 30, 127128 (2020)

 

E.Baş et al.

ADP-Ribose and oxidative stress activate TRPM8 channel in prostate cancer and kidney cells.

Scientific Reports 9, 4100 (2019)

 

M.Poreba et al.

Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells.

Cell Death & Differentiation 26, 2695-2709 (2019)