CLEAR: A novel family of highly cross-linked polymeric supports for solid-phase peptide synthesis
CLEAR: A novel family of highly cross-linked polymeric supports for solid-phase peptide synthesis
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DOI：
10.1021/ja954196s
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发表时间：
1996-07-31
影响因子：
15
通讯作者：
Barany, G
中科院分区：
文献类型：
--
作者：
Kempe, M;Barany, G
交联的乙氧基丙烯酸酯树脂（CLEAR）载体通过支化交联剂三甲基丙烷乙氧基化物（14/3EO/OH）三丙烯酸酯（1）与烯丙基胺（2）、甲基丙烯酸2-氨基乙酯（2-aminoethyl methacrylate）中的一种或多种以本体或悬浮模式进行自由基共聚来制备。HCl（3）、聚（乙二醇-400）二甲基丙烯酸酯（4）、聚（乙二醇）乙基醚甲基丙烯酸酯（5）和三甲基丙烷三甲基丙烯酸酯（6）。将通过本体程序得到的高度交联的共聚物研磨并筛分成颗粒，而悬浮聚合程序得到高度交联的球形珠状载体。CLEAR聚合物载体在包括水、醇、四氢呋喃、二氯甲烷和N，N-二甲基甲酰胺在内的非常广泛的溶剂中显示出优异的溶胀性能。为了证明它们对肽合成的有用性，CLEAR支持物用“内部参考”氨基酸[正亮氨酸]和手柄[5-氨基-2-甲基（4-Fmoc-氨基甲基-3，5-二甲氧基苯氧基）戊酸]，并测试了挑战性肽如酰基载体蛋白（65-74）、逆酰基载体蛋白（74-65）、和17肽人胃泌素-I。与市售载体的比较，例如，聚苯乙烯，Pepsyn K.还进行了Polyhipe、PEG-PS、TentaGel和PEGA。CLEAR载体在肽合成的标准条件下是完全稳定的，但在某些情况下对某些强碱不稳定。
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.