Following preliminary reports that introduced 4-tert-butylbenzhydrylamine resin (BUBHAR) as a novel polymer for use in solid-phase peptide chemistry (SPPS), some physical-chemical properties of its structure, certainly relevant for its application in this methodology, were compared with those of the largely used methylbenzhydrylamine resin (MBHAR). In order to rule out possible MBHAR-related commercial source effects for SPPS, we initially compared MBHAR batches acquired from three different manufacturers with homemade BUBHARs. The bead solvation properties of these two resins in solvents used in the tert-butyl (Boc-based) SPPS technique indicated that the mean swelling values of these solid supports (% volume of solvated bead occupied by the solvent) were 51% and 67% for MBHAR and BUBHAR, respectively. This result strongly suggests a good potential for the latter polymer in terms of application for application in SPPS. In order to move forward with this approach, the synthesis of the carboxy-terminal peptide fragment (Gln-Asn-Cys-Pro-(D-Arg)-Gly-amide) of the antidiuretic hormone, desmopressin ([3-Mpa-Tyr-Phe-Gln-Asn-Cys-Pro-(D-Arg)-Gly-amide], 1-[3-mercaptopropionic acid]), which our laboratory is producing routinely in large scale for the Health Secretary of Sao Paulo State. The comparative synthesis was conducted using these two resins with similar substitution degrees (~0.7 mmol/g). In contrast to MBHAR, surprisingly no need for a Gln⟶Asn recoupling reaction was observed when BUBHAR was used. This result might be due to improved solvation of the desmopressin C-terminal Asn-Cys-Pro-(D-Arg)-Gly-segment when bound to this latter resin as observed by microscopic swelling degrees of peptide-resin beads and also by greater mobility detected of peptide chains within the BUBHAR polymer backbone. This finding was determined by comparative electron paramagnetic resonance (EPR) of both peptide resins attaching the amino acid-type paramagnetic 2.2.6.6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (Toac) spin label early introduced by our group.

中文翻译：

---

评价4-叔丁基苄基苯胺树脂（BUBHAR）作为肽合成的另一种固体支持物

在初步报告中介绍了4-叔丁基苯甲胺树脂（BUBHAR）作为用于固相肽化学（SPPS）的新型聚合物之后，比较了其结构的某些物理化学性质，这些化学性质肯定与其在该方法学中的应用有关以及大量使用的甲基苯甲胺树脂（MBHAR）的产品。为了排除SPPS可能与MBHAR相关的商业来源影响，我们首先比较了从三个不同制造商处获得的MBHAR批次与自制的BUBHAR。在溶剂中所使用的这些两种树脂的胎圈溶剂化性质叔丁基（基于Boc的）SPPS技术表明，对于MBHAR和BUBHAR，这些固体支持物的平均溶胀值（溶剂占溶剂化珠粒的体积百分比）分别为51％和67％。该结果强烈暗示了后者聚合物在SPPS中的应用方面具有良好的潜力。为了用这种方法向前发展，合成了抗利尿激素去氨加压素（[3-Mpa - Tyr]的羧基末端肽片段（Gln-Asn-Cys-Pro-（D-Arg）-Gly-amide）-Phe-Gln-Asn-Cys-Pro-（D-Arg）-Gly-amide]，1- [3-巯基丙酸]），这是我们实验室为圣保罗州卫生大臣常规生产的常规产品。使用这两种树脂具有相似的取代度（〜0.7 mmol / g）进行比较合成。与MBHAR相比，令人惊讶的是，当使用BUBHAR时，无需进行Gln⟶Asn再偶联反应。这个结果可能是由于去氨加压素C末端Asn-Cys-Pro-（D-Arg）-Gly-segment与后一种树脂结合时溶剂化的改善，如通过肽树脂珠的微观溶胀度观察到的，以及在BUBHAR聚合物主链中检测肽链的迁移率。这个发现是通过两种氨基酸与顺磁性2.2.6的肽树脂的比较电子顺磁共振（EPR）确定的。