Cross-Linked Ethoxylate Acrylate Resin (CLEAR) supports were prepared by radical copolymerization, either in the bulk or suspension mode, of the branched cross-linker trimethylolpropane ethoxylate (14/3 EO/OH) triacrylate (1) with one or more of allylamine (2), 2-aminoethyl methacrylate·HCl (3), poly(ethylene glycol-400) dimethacrylate (4), poly(ethylene glycol) ethyl ether methacrylate (5), and trimethylolpropane trimethacrylate (6). The resultant highly cross-linked copolymers by the bulk procedures were ground and sieved to particles, whereas the suspension polymerization procedure gave highly cross-linked spherical beaded supports. CLEAR polymeric supports showed excellent swelling properties in an unusually broad range of solvents, including water, alcohols, tetrahydrofuran, dichloromethane, and N,N-dimethylformamide. To demonstrate their usefulness for peptide synthesis, CLEAR supports were derivatized with an “internal reference” amino acid [norleucine] and a handle [5-(4-Fmoc-aminomethyl-3,5-dimethoxyphenoxy)valeric acid] and were tested for both batchwise and continuous-flow solid-phase syntheses of challenging peptides such as acyl carrier protein (65-74), retro-acyl carrier protein (74-65), and the 17-peptide human gastrin-I. Comparisons to commercially available supports, e.g., polystyrene, Pepsyn K, Polyhipe, PEG-PS, TentaGel, and PEGA were also carried out. CLEAR supports are entirely stable under standard conditions of peptide synthesis but are in some cases labile to certain strong bases. (J. Am. Chem. Soc. 1996, 118, 30, 7083–7093.)
SPOCC resin 1, a novel, highly permeable, polar support for chemical and enzymatic solid-phase methods, is presented. The synthesis of SPOCC resin is based on the cross-linking of long-chain poly(ethylene glycol) (PEG) terminally substituted with oxetane by cationic ring-opening polymerization, affording a polymer containing only primary ether and alcohol C−O bonds. The polymer was prepared using Et2O·BF3 as initiator either via bulk polymerization in solution or via suspension polymerization in silicon oil, the latter yielding a beaded resin. The polymerization reaction was investigated with respect to the effects of PEG chain length, the fraction of bisoxetanylated PEG, initiator amount, and temperature in order to vary the swelling, loading, and mechanical stability of the resin. Furthermore, the resin was derivatized with various functional groups and subsequently applied to peptide synthesis and organic reactions in both organic solvents and water. An N-terminal peptide aldehyde was generated on the solid phase and employed to synthesize peptide isosteres by nucleophilic addition of various ylides. Solid-phase glycosylation of peptides and enzymatic reactions were successfully performed with SPOCC resin. Enzymatic proteolytic cleavage of a resin-bound decapeptide on treatment with the 27 kDa protease subtilisin BNP‘ demonstrated the accessibility of the interior of the SPOCC resin for enzymes. (J. Am. Chem. Soc. 1999, 121, 23, 5459–5466.)
In the 1980s, virus inactivation steps were implemented into the manufacturing of biopharmaceuticals in response to earlier unforeseen virus transmissions. The most effective inactivation process for lipid-enveloped viruses is the treatment by a combination of detergents, often including Triton X-100 (TX-100). Based on recent environmental concerns, the use of TX-100 in Europe will be ultimately banned, which forces the pharmaceutical industry, among others, to switch to an environmentally friendly alternative detergent with fully equivalent virus inactivation performance such as TX-100. In this study, a structure–activity relationship study was conducted that ultimately led to the synthesis of several new detergents. One of them, named “Nereid,” displayed inactivation activity fully equivalent to TX-100. The synthesis of this replacement candidate has been optimized to allow for the production of several kg of detergent at lab scale, to enable the required feasibility and comparison virus inactivation studies needed to support a potential future transition. The 3-step, chromatography-free synthesis process described herein uses inexpensive starting materials, has a robust and simple work-up, and allows production in a standard organic laboratory to deliver batches of several hundred grams with >99% purity.
To minimize the risk of transmitting infectious lipid-enveloped viruses like the hepatitis B or C viruses (HBV, HCV), Human immunodeficiency virus (HIV), and also emerging and unknown viruses, S/D treatment is still recognized as the most effective and robust method.3 Frequently, this mild chemical treatment contains a mixture of the non-ionic detergent TX-100 (I), tri-n-butyl-phosphate (TNBP), and often also Polysorbate 80 (PS80). (J Med Virol. 2021;93:3880–3889.)