Macromolecular Function Emerging from Intramolecular Peptide Stapling of Synthetic Polymers.

IF 4.2 3区 化学 Q2 POLYMER SCIENCE Macromolecular Rapid Communications Pub Date : 2024-10-22 DOI:10.1002/marc.202400591
Henrik Kalmer, Federica Sbordone, John McMurtrie, Christoph Nitsche, Hendrik Frisch
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Abstract

Protein function results from the precise folding of polypeptides into bespoke architectures. Taking inspiration from nature, the field of single-chain nanoparticles (SCNPs), intramolecularly crosslinked synthetic polymers, emerged. In contrast to nature, the function of SCNPs is generally defined by the parent polymer or the applied crosslinker, rather than by the crosslinking process itself. This work explores the cyanopyridine-aminothiol click reaction to crosslink peptide-decorated polymers intra-macromolecularly to endow the resulting SCNPs with emerging functionality, resulting from the conversion of N-terminal cysteine units into pyridine-thiazolines. Dimethylacrylamide based polymers with different cysteine-terminated amino acid sequences tethered to their sidechains are investigated (P1 (C), P2 (GDHC), P3 (GDSC)) and intramolecularly crosslinked into SCNPs. Since the deprotection of the parent polymers yields disulfide-based SCNPs, a direct comparison between disulfide and pyridine-thiazolines crosslinked SCNPs is possible. This comparison revealed two emerging properties of the pyridine-thiazoline crosslinked SCNPs: 1) The formation of pyridine-thiazolines gave rise to metal binding sites within the SCNP, which complexed iron. 2) Depending on the peptide sequence in the precursor polymer, the hydrolytic activity of the peptide sequences is either increased (GDHC) or decreased (GDSC) upon pyridine-thiazoline formation compared to identical SCNPs based on disulfide crosslinks.

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合成聚合物分子内肽键合产生的大分子功能。
蛋白质的功能源于多肽精确折叠成定制结构。从大自然中汲取灵感,单链纳米粒子(SCNPs)--分子内交联合成聚合物领域应运而生。与自然界不同的是,SCNPs 的功能通常由母体聚合物或应用的交联剂决定,而不是由交联过程本身决定。这项研究探索了氰基吡啶-氨基硫醇点击反应,通过将 N 端半胱氨酸单元转化为吡啶-噻唑啉,在分子内交联肽装饰聚合物,从而赋予 SCNPs 新的功能。我们研究了以二甲基丙烯酰胺为基础的聚合物(P1 (C)、P2 (GDHC)、P3 (GDSC)),这些聚合物的侧链系有不同的半胱氨酸末端氨基酸序列,并在分子内交联成 SCNP。由于母体聚合物的脱保护作用会产生基于二硫化物的 SCNPs,因此可以对二硫化物和吡啶-噻唑交联 SCNPs 进行直接比较。这种比较揭示了吡啶-噻唑啉交联 SCNP 的两个新特性:1)吡啶-噻唑啉的形成在 SCNP 中产生了金属结合位点,从而与铁发生络合。2)根据前体聚合物中的肽序列,与基于二硫交联的相同 SCNP 相比,吡啶-噻唑啉形成后,肽序列的水解活性会增加(GDHC)或降低(GDSC)。
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来源期刊
Macromolecular Rapid Communications
Macromolecular Rapid Communications 工程技术-高分子科学
CiteScore
7.70
自引率
6.50%
发文量
477
审稿时长
1.4 months
期刊介绍: Macromolecular Rapid Communications publishes original research in polymer science, ranging from chemistry and physics of polymers to polymers in materials science and life sciences.
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