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Peptide Handbook

Click Peptide Synthesis Service

O-acyl bond incorporation technology

Increases peptide solubility, decreases aggregation

Powerful tool for β-amyloid research

Click Peptide Service

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Hydrophobic peptides are difficult to prepare and handle, making their study or use in biological research difficult. For example, β-amyloids, which are highly hydrophobic peptides, are prone to natural self-assembly. These peptides aggregate and deposit on organs, forming debilitating plaques that are involved in the progression of many neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as other diseases such as diabetes and Huntington's. β-amyloids are targets for developing effective therapies to treat these diseases, but these studies are often hindered by uncontrollable aggregative nature of β-amyloids.

Services Features

Key Features

1. Click Peptide Synthesis allows control over

Physicochemical peptide properties (e.g., water-solubility, self-assembly, aggregation, or folding)
Biologic activities (e.g., ligand-receptor binding affinity, or enzyme-substrate binding affinity)

2. Control over Click Peptide to native peptide conversion

Click peptide converts to native peptide easily at pH 7.4 or above
Conversion is a one-way, quick process
No by-product formation during conversion, suitable for biological experiments

Key Advantages

Increases peptide solubility
Slows peptide aggregation
Novel system useful for investigating the dynamic biological functions of β-amyloids in neurodegenerative diseases and other diseases exhibiting amyloidosis

References

Atsuhiko Taniguchi, Youhei Sohma, et al. Click peptide: Chemical Biology-oriented analogues of Alzheimer's amyloid β peptide 1–42. J. Peptide Science. Nov 2006; 12(12): 823-828

Youhei Sohma, Atsuhiko Taniguchi, et al. Controlled Production of Amyloid β Peptide from a Photo-Triggered, Water-Soluble Precursor "Click Peptide". ChemBioChem. Nov 2008; 9(18): 3055-3065

Hui Wang, Taeko Kakizawa, et al. Synthesis of amyloid β peptide 1–42 (E22Δ) click peptide: pH-triggered in situ production of its native form. Bioorganic & Medicinal Chemistry. July 2009; 17(14): 4881-4887

Taniguchi A, Kiso Y, et al. "Click peptide": pH-triggered in situ production and aggregation of monomer Abeta1-42. ChemBioChem. Mar 2009; 10(4): 710-715

Claudia Balducci, Marten Beeg, et al. Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein. PNAS. Jan 2010; doi:10.1073

Principle

Our Click Peptides are synthesized using the O-acyl isopeptide method, which was developed by Taniguchi, et al (Figure 1). We use a special synthesis method to incorporate a strategically placed o-acyl bond in place of a naturally occurring n-acyl bond in the native peptide. The resulting peptide, called an o-acyl isopeptide, exhibits enhanced solubility and minimal peptide self-assembly, due to a reduction in intramolecular hydrogen bond interactions between peptide chains.
Adjusting the pH of the Click Peptide solution to ≥7.4 induces a rapid O→N intermolecular acyl migration (conversion of O-acyl bond to N-acyl bond), which rapidly converts the insoluble Click Peptide to its soluble native form. No byproduct is released when the Click Peptide is converted to the native peptide, making it advantageous for in vitro and in vivo biological experimental systems.

Figure 1: Conversion of Click Peptide to native peptide via pH change

Reference

Atsuhiko Taniguchi, Youhei Sohma, et al. Click peptide: Chemical Biology-oriented analogues of Alzheimer's amyloid β peptide 1–42. J. Peptide Science. Nov 2006; 12(12): 823-828

Case Study

26-O-acyl β-amyloid (1-42) click peptide was successfully synthesized, the β-ester bond in which can be quickly and quantitatively converted to a native Gly²⁵-Ser²⁶ amide bond via a pH-dependent O-N intramolecular acyl migration reaction (t_1/2 =1 min, pH 7.4, 37℃) at a hydroxyamino acid residue. Namely, upon this pH-triggered conversion (pH-click), the non-aggregative and water-soluble precursor (click peptide) can produce the monomer with a random-coil structure under physiological conditions (pH 7.4, 37℃). The structure information is as follows.

Scheme 2: β-amyloid (1-42) click peptide

Result

β-amyloid precursor(click peptide) has a water solubility of 15 mg/ml, while it is only 0.14 mg/ml for the native peptide.
The aggregative property of the peptides reduced significantly.
The O-acyl moiety was stable under acidic pH.

The following are HPLC reports of (Scheme 3) purified β-amyloid (1-42) native peptide converted from β-amyloid (1-42) click peptide (precursor) and (Scheme 4) purified 26-O-acyl β-amyloid (1-42) click peptide (precursor).

(Scheme 3) HPLC report of purified β-amyloid (1-42) native peptide converted from β-amyloid (1-42) click peptide (precursor)

(Scheme 4) HPLC report of purified 26-O-acyl β-amyloid (1-42) click peptide (precursor)

Quotations and Ordering

For quotations, please use our Secure Instant Online Quotation/Order system. However, you may also contact us by email, phone (1-732-885-9188), fax (1-732-210-0262), or via our Secure Messaging System.
Order can be placed by email, phone, or fax with either a PO (Purchase Order) or credit card. Please submit your peptide sequence at peptide@genscript.com using our Click Peptide Order Form.
We accept POs and major credit cards (). A 7% New Jersey sales tax will be applied to orders shipped to New Jersey. Your credit card will be billed under "GenScript" Click here to download our credit reference form. For international orders, we must apply the full charge at the time the order is placed. In the unlikely event that any given order cannot be filled, our guarantee will take the form of a full refund.

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