Clauss Zachary S, Kramer Jessica R
Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah 84112, United States.
ACS Appl Mater Interfaces. 2021 Dec 30. doi: 10.1021/acsami.1c19692.
Peptoids have attracted attention for application in biomedicine due to their advantageous properties as compared to peptides. The structural analogues are typically resistant to protease degradation and offer improved biocompatibility. Chemical routes to an impressive variety of short-chain, low-molecular-weight peptoids are well-established. However, synthetic methods for well-defined, high-molecular-weight polypeptoids with side chain diversity are still in their infancy. Here, we report a facile method for synthesis of polypeptoids via transition-metal-catalyzed controlled, living polymerization of -substituted -carboxyanhydrides. Our method is amenable to hydrophilic and hydrophobic side chains and yields high-molecular-weight linear polypeptoids of predictable length and low dispersity. Further, the polymer end groups can be tuned for biological targeting, and polypeptide-polypeptoid hybrids are readily prepared in one pot. Our materials are indeed resistant to common proteases and are well-tolerated by human cells. Overall, this work represents a significant stride toward access to tunable polypeptoids.
与肽相比，类肽因其具有优势特性而在生物医学应用中受到关注。这些结构类似物通常对蛋白酶降解具有抗性，并具有更好的生物相容性。合成各种令人印象深刻的短链、低分子量类肽的化学路线已经很成熟。然而，用于合成具有侧链多样性的明确的高分子量聚类肽的方法仍处于起步阶段。在此，我们报道了一种通过过渡金属催化的α-取代的α-羧酸酐的可控活性聚合来合成聚类肽的简便方法。我们的方法适用于亲水性和疏水性侧链，并能产生具有可预测长度和低分散度的高分子量线性聚类肽。此外，聚合物端基可用于生物靶向的调节，并且可以在一锅法中轻松制备多肽-聚类肽杂化物。我们的材料确实对常见蛋白酶具有抗性，并且能被人类细胞良好耐受。总体而言，这项工作朝着获得可调节的聚类肽迈出了重要一步。
