Month: June 2022

CLEAR:  A Novel Family of Highly Cross-Linked Polymeric Supports for Solid-Phase Peptide Synthesis

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:  A Resin for Solid-Phase Organic Chemistry and Enzymatic Reactions on Solid Phase

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.)