Judge Nicola, Heise Andreas
Department of Chemistry, RCSI University of Medicine and Health Sciences, Dublin D02 YN77, Ireland.
Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CURAM), RCSI, Dublin D02 YN77, Ireland.
Macromolecules. 2024 Feb 27;57(5):1979-1987. doi: 10.1021/acs.macromol.3c02538. eCollection 2024 Mar 12.
Homopolymerization of ortho-nitrobenzyl (NB)-protected l-cysteine and l-glutamic acid was systematically studied in different solvents and at different monomer to initiator ratios, revealing the best reaction control in dimethylformamide (DMF) across a range of degrees of polymerization. In the subsequent ultraviolet (UV)-cleavage studies, it was found that quantitative deprotection upon UV exposure at 365 nm was not achievable for either of the homopolypeptides as confirmed by H NMR and UV/visible (UV/vis) analyses. While the poly(NB-l-cysteine) deprotected more readily with no effect of the polypeptide molecular weight, lower molecular weight poly(NB-l-glutamate) reached maximum deprotection faster than high molecular weight samples. This was further confirmed by the pH changes of the solution. When incorporated into the core of miniemulsion-derived nanoparticles, both NB-protected copolypeptides were successfully deprotected as evident from a color change and a pH change in the case of poly(NB-l-glutamate). However, the removal of the deprotection byproduct nitrosobenzaldehyde proved unsuccessful, which indicates a diffusion barrier caused by the nanoparticle's surfactant. The study provides insights and guidelines for the UV deprotection of polypeptides and demonstrates the ability to selectively UV-deprotect polypeptides in the confined space of a nanoparticle dispersion.
对邻硝基苄基（NB）保护的L-半胱氨酸和L-谷氨酸的均聚反应在不同溶剂和不同单体与引发剂比例下进行了系统研究，结果表明，在一系列聚合度范围内，二甲基甲酰胺（DMF）中的反应控制效果最佳。在随后的紫外（UV）裂解研究中，通过核磁共振氢谱（H NMR）和紫外/可见（UV/vis）分析证实，两种均聚物多肽在365 nm紫外光照射下均无法实现定量脱保护。虽然聚（NB-L-半胱氨酸）更容易脱保护，且不受多肽分子量的影响，但低分子量的聚（NB-L-谷氨酸）比高分子量样品更快达到最大脱保护程度。溶液的pH变化进一步证实了这一点。当将两种NB保护的共聚多肽掺入微乳液衍生的纳米颗粒核心时，如聚（NB-L-谷氨酸）的情况，通过颜色变化和pH变化可以明显看出两种多肽都成功脱保护。然而，去除脱保护副产物亚硝基苯甲醛的尝试未成功，这表明纳米颗粒表面活性剂造成了扩散障碍。该研究为多肽的紫外脱保护提供了见解和指导，并证明了在纳米颗粒分散体的受限空间中选择性紫外脱保护多肽的能力。
