Switchable Coacervate Formation via Amino Acid Functionalization of Poly(dehydroalanine)
Switchable Coacervate Formation via Amino Acid Functionalization of Poly(dehydroalanine)
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DOI：
10.1021/acs.biomac.4c00048
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发表时间：
2024-03-01
影响因子：
6.2
通讯作者：
Deming，Timothy J.
中科院分区：
文献类型：
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作者：
Morrison，Casey A.;Chan，Ethan P.;Deming，Timothy J.
我们的小组最近开发了一个家族的侧链氨基酸官能化的聚（S-烷基-l-同型半胱氨酸），Xaa-CH（Xaa =通用氨基酸），其具有在水中形成环境响应凝聚体的能力。为了进一步研究分子结构对多肽凝聚体形成的影响，我们通过对聚脱氢丙氨酸（ADH）进行后聚合改性，制备了侧链氨基酸功能化的聚（S-烷基-rac-半胱氨酸）（Xaa-rac-C）。ADH平台的使用允许通过未保护的1-氨基酸2-巯基乙基酰胺与ADH的直接反应直接合成各种侧链氨基酸官能化的多肽。尽管它们的主链结构不同，我们发现thatXaa-rac-C可以形成凝聚体的性质类似于与Xaa-CH。这些结果表明，侧链氨基酸的多肽的掺入可能是一种方式，一般有利于凝聚。在Met-rac-Calle中掺入甲硫氨酸使得能够制备对高离子强度介质具有改善的稳定性的凝聚体。此外，在Met-rac-C中存在额外的硫醚基团导致在氧化时增加的溶解度变化，从而允许在水性介质中形成凝聚层的容易的可逆氧化还原转换。
Our group recently developed a family of side-chain amino acid-functionalized poly(S-alkyl-l-homocysteines),Xaa-CH(Xaa = generic amino acid), which possess the ability to form environmentally responsive coacervates in water. In an effort to further study how the molecular structure affects polypeptide coacervate formation, we prepared side-chain amino acid-functionalized poly(S-alkyl-rac-cysteines),Xaa-rac-C, via post-polymerization modification of poly(dehydroalanine),ADH. The use of theADHplatform allowed straightforward synthesis of a diverse range of side-chain amino acid-functionalized polypeptides via direct reaction of unprotectedl-amino acid 2-mercaptoethylamides withADH. Despite their differences in the main-chain structure, we found thatXaa-rac-Ccan form coacervates with properties similar to those seen withXaa-CH. These results suggest that the incorporation of side-chain amino acids onto polypeptides may be a way to generally favor coacervation. The incorporation ofl-methionine inMet-rac-Callowed the preparation of coacervates with improved stability against high ionic strength media. Further, the presence of additional thioether groups inMet-rac-Cresulted in an increased solubility change upon oxidation allowing facile reversible redox switching of coacervate formation in aqueous media.