A novel tri(propylene glycol) glycerolate diacrylate cross-linked polystyrene support for solid phase peptide synthesis was prepared by aqueous radical suspension polymerization. The peptides were grown from the hydroxy functionality of the cross-linker in the polymer and this makes it unique among other styrene-based polymer supports that are currently used in polypeptide synthesis. The role of the polymer support in peptide synthesis was established by studies delineating the optimization of synthetic steps involved in solid phase synthesis. The optimization studies include C-terminal amino acid incorporation, N^α-Fmoc and Boc-deprotection, acylation reactions and the removal of the target peptide from the support. The dependence between the nature and extent of cross-linking of the polymer backbone and the reactivity of the attached amino groups was investigated by carrying out a reactivity study on amide bond formation compared with Merrifield resin. The resin-like behavior of the new support was studied by synthesizing a ‘difficult’ sequence of the (34–42) fragment of β-amyloid peptide (1–42) and compared with commercially available Merrifield and Sheppard resins. The synthetic utility of the support was established by synthesizing a 23-residue NR 2B peptide substrate of Ca²⁺/calmodulin binding peptide in high yield and purity. Better solvation of the resin beads, enhanced coupling efficiency in the peptide synthetic steps and the high yield and purity of the peptides synthesized highlights the positive role of the cross-linker in the new polystyrene support.

中文翻译：

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三（丙二醇）甘油三酸酯二丙烯酸酯交联聚苯乙烯树脂在多肽合成中的合成与优化：高分子支持物在固相肽合成中的作用

通过水基自由基悬浮聚合反应制备了用于固相肽合成的新型三（丙二醇）甘油酸酯二丙烯酸酯交联聚苯乙烯载体。肽从聚合物中交联剂的羟基官能团生长而来，这使其在多肽合成中目前使用的其他基于苯乙烯的聚合物载体中独树一帜。通过描述固相合成中涉及的合成步骤的优化研究，确立了聚合物载体在肽合成中的作用。优化研究包括Ç端氨基酸掺入，Ñ ^α-Fmoc和Boc脱保护，酰化反应以及从支持物上去除目标肽。与Merrifield树脂相比，通过对酰胺键形成的反应性研究，研究了聚合物主链交联的性质和程度与连接的氨基的反应性之间的依赖性。通过合成β-淀粉样肽（1-42）的（34-42）片段的“困难”序列来研究新支持物的树脂状行为，并与市售的Merrifield和Sheppard树脂进行了比较。支持物的合成用途是通过合成23个残基的Ca ²⁺ NR 2B肽底物来建立的/钙调蛋白结合肽的产率高和纯度高。树脂珠粒的更好的溶剂化，肽合成步骤中增强的偶联效率以及合成的肽的高收率和纯度突出了交联剂在新型聚苯乙烯载体中的积极作用。