Abstract：
In recent years, there has been a growing focus on the development of medium-sized drugs based on peptides or nucleic acids owing to their potential therapeutic benefits. As some of these medium-sized drugs exert their therapeutic effects by adopting specific secondary structures, evaluating their conformational states is crucial to ensure the efficacy, quality, and safety of the drug products. It is important to assess the structural integrity of biomolecular therapeutics to guarantee their intended pharmacological activity and maintain the required standards for drug development and manufacturing. One widely utilized technique for quality evaluation is secondary structural analysis using circular dichroism (CD) spectroscopy. Given the higher production and quality control costs associated with medium-sized drugs compared with small-molecule drugs, developing analytical techniques that enable CD analysis with reduced sample volumes is highly desirable. Herein, we focused on a microsampling disk-type cell as a potential solution for reducing the required sample volume. We investigated whether CD spectral analysis using a microsampling disk could provide equivalent spectra compared with the standard cell (sample volume: approx. 300 µL). Our findings demonstrated that the microsampling disk (sample volume: 2-10 µL) could be successfully applied to CD spectral analysis of peptide and nucleic acid drugs, paving the way for more efficient and cost-effective quality evaluation processes.
摘要：
近年来,基于肽或核酸的中等大小的药物的开发由于其潜在的治疗益处而日益受到关注。由于这些中型药物中的一些通过采用特定的二级结构来发挥其治疗作用，评估它们的构象状态对于确保功效至关重要，质量,以及药品的安全性。重要的是评估生物分子治疗剂的结构完整性以保证其预期的药理学活性并维持药物开发和制造所需的标准。一种广泛使用的质量评估技术是使用圆二色性（CD）光谱法的二级结构分析。鉴于与小分子药物相比，中型药物的生产和质量控制成本更高，开发能够减少样品体积的CD分析的分析技术是非常可取的。在这里，我们专注于微量采样圆盘型细胞，作为减少所需样本量的潜在解决方案。我们调查了使用微量采样盘进行CD光谱分析是否可以提供与标准单元（样品体积：约。300微升)。我们的发现表明，微采样盘（样品体积：2-10µL）可以成功地应用于肽和核酸药物的CD光谱分析，为更有效和更具成本效益的质量评估过程铺平道路。
