Amino-Li Resin – A Novel Solid Support

The so-called solid-phase peptide synthesis (SPPS) allows to grow a peptide chain step by step on a specialized solid support and thus the removal of unreacted entities by washing. For the synthesis in organic solvents, a variety of polystyrene resins is on the market. In contrast, for applications in aqueous media, there is only a limited number of choices, especially since the well-established PEG-based ChemMatrix® resin was discontinued. Facing the tougher restrictions on DMF and the aim to develop “greener” approaches using solvents which are permitting to reduce the risks for the environment and for human health, researchers are eagerly looking for novel resins – besides TentaGel® – which are compatible with water.

(Amino-)Li resin, named after its inventor Dr. Yongfu Li, is a novel high-performance poly-acrylamide solid support suitable for the synthesis of peptides and other biomolecules. It is characterized by a high swelling factor and high polarity making it the perfect candidate for synthesis in water, e.g. in combination with Smoc amino acids, but not limited to it. For polar solvents, the swelling is reported with about 6 ml/g in DMF, DMSO and NBP, about 7 ml/g in water, and about 8 ml/g in DCM, but the resin is also compatible with some non-polar reaction media.

Li resin is made from N,N-dimethyl(acrylamide) cross-linked with N,N'-bis(acryloyl)piperazine and functionalized with 1-[1-(N-acrylyl)piperidin-4-yl]methanamine. The polymerization uses a proprietary technology to produce fibers similar in size to bead resins but with a larger surface area. The resin structure was selected to obtain a loading of around 0.5 mmol/g.

Chemical structures of Li resin and its starting materials.

The aliphatic aminomethylpiperidine moiety of the Li resin is more reactive than the benzhydrylamine or benzylamine used in most polystyrene-based resins, thus facilitating the incorporation of a linker to the resin via an amide bond. In addition, this aliphatic amide is more stable to the acidic conditions required during the final deprotection and cleavage step than aromatic amides.

As reported in literature, a Rink linker, for example, can be introduced to the solid support in DMF under HBTU/DIEA activation followed by Fmoc cleavage with 20% piperidine in water. The dried Rink-Amide Li resin demonstrates good swelling behavior in water. Depending on your needs, we can derivatize and functionalize the Amino-Li resin for you as custom synthesis. Get in contact! 

Schematic illustration of a peptide synthesized on Amino-Li resin. The amino acid chain is built on a Rink Amide-linker (RL-1027) attached to the ethylamino function of the resin.

Mechanically, acrylamide-based resins are in general less robust than those with a polystyrene core. Therefore, Li resin suspensions should be gently shaken and drained by gravity, as the forces of mechanical stirring and vacuum filtration tend to collapse the fibers and the resulting fines can affect the rheological properties of the resin and clog the frit.

Further potential applications of the Li resin as solid support include affinity chromatography and reactions with immobilized enzymes, as an alternative to agarose-based matrices. In contrast to the latter ones, where activated carboxy groups are used to immobilize the ligand, Li resin allows the immobilization on the primary amino groups of the aminomethylpiperidine moieties.

→ Interested in Smoc peptide synthesis using Li resin? Read this publication! 

→ For more information on the Smoc technology, download our flyer! 

→ Looking for a general overview of Resins? See our booklet! 

References:

A Practical Peptide Synthesis Workflow Using Amino-Li-Resin; D. C. Akintayo, S. Rao Manne, B. G. de la Torre, Y. Li, F. Albericio; Methods Protoc. 2022; 5(5): 72-84. https://doi.org/10.3390%2Fmps5050072

Amino-Li-Resin-A Fiber Polyacrylamide Resin for Solid-Phase Peptide Synthesis; D. C. Akintayo, B. G. de la Torre, Y. Li, F. Albericio; Polymers (Basel) 2022; 14(5): 928- 942. https://doi.org/10.3390/polym14050928

Novel amino-Li resin for water-based solid-phase peptide synthesis; C. Uth, S. Englert, O. Avrutina, H. Kolmar, S. Knauer; J Pept. Sci. 2023; 29(12): e3527. https://doi.org/10.1002/psc.3527