Matthews, North Carolina – CEM Corporation, a leading supplier of microwave peptide synthesizers and reagents, is pleased to introduce a new universal loading resin for the generation of c-terminal peptide acids in solid phase peptide synthesis (SPPS). By using a new trityl dichloroacetate (TRT-DCA) linker variant, this novel resin eliminates the need for pre-loaded resins containing the first amino acid in c-terminal peptide acid synthesis. In contrast to traditional linkers used for this type of synthesis, TRT-DCA allows a simple attachment of any amino acid, eliminating the need to inventory all 20 pre-loaded resins, while still maintaining high stability towards hydrolysis1.

TRT-DCA SpheriTide Resin

Historically, loading the first amino acid onto a linker providing a c-terminal acid (Wang, HMPA) is difficult due to the need for a hydroxyl group to act as a nucleophile. Special conditions are required which can lead to side reactions, including epimerization, dipeptide formation, and incomplete loading. Therefore, resins with acid type linkages are typically produced with the first amino acid already attached. As an advantage, hyper-acid sensitive linkers (2-Cl-trityl, trityl) provide easier loading in an available chlorinated form, however this form is sensitive to hydrolysis, limiting stability for longer term use.

The TRT-DCA linker provides a more stable form towards hydrolysis with a loading procedure similar to hyper-acid sensitive resins in a chlorinated form. Upon addition of the first amino acid, a trityl linkage is maintained throughout the peptide synthesis process. Advantageously, the bulky nature of the trityl linker minimizes diketopiperazine and 3-(1-piperidinyl)alanine formation, compared to Wang/HMPA type linkages. Additionally, the hyper-acid sensitive nature of the trityl linker allows for a fully protected peptide to be generated at the end of the synthesis through use of an appropriate cleavage cocktail.

The use of hyper-acid sensitive resins has typically been limited to moderate temperatures, due to risks of premature cleavage from the resin. Recently, CEM introduced a new carbodiimide based method that allows for high yield of trityl based resins at 90°C using high-efficiency solid phase peptide synthesis (HE-SPPS™)2 methods. This methodology was found to increase peptide purity over any existing activation method at elevated temperatures while also providing advantages for sensitive sequences such as phosphopeptides. Together, the new TRT-DCA SpheriTide® resin and the new carbodiimide coupling method allow peptide chemists to fully exploit the benefits of HE-SPPS with a universal loading, hyper-acid sensitive resin for c-terminal peptide acids.

Jonathan M. Collins, Director of Business Development for CEM Corporation commented: “The combination of the TRT-DCA SpheriTide resin with the newly developed carbodiimide coupling methods is very useful for simplifying and improving peptide synthesis at elevated temperatures. Not only does this eliminate the need to purchase pre-loaded acid resins, but also improves peptide purities while providing inherent protection against common c-terminal side reactions.” CEM’s Liberty Blue™ Peptide Synthesizer now includes an automated standard method for TRT-DCA SpheriTide resin loading. Trityl-DCA SpheriTide resin is available for purchase at the CEM Corporation online store.

References:

1Worldwide patents pending

2Worldwide patents pending; Presented at the 12th German Peptide Symposium in Darmstadt, Germany

SpheriTide® is a registered trademark of Spheritech Ltd., is patented under PCT/EP2012/057264 and exclusively licensed by CEM Corporation.

CEM Corporation, a private company based in Matthews, North Carolina, is a leading provider of scientific solutions for critical laboratory applications. The Company has subsidiaries in the United Kingdom, Germany, Italy, France, and Japan, as well as a global network of distributors. CEM designs and manufactures systems for life sciences, analytical laboratories and processing plants worldwide. The Company’s products are used in many industries including pharmaceutical, biotech, chemical and food processing, as well as academic research.