Schmerberg Claire M, Li Lingjun
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Protein Pept Lett. 2013 Jun;20(6):681-94. doi: 10.2174/0929866511320060007.
A number of unique challenges are inherent to the study of neuropeptides (NPs), both in determining their molecular structure and their function. Traditional studies follow a model in which novel NPs are discovered and identified, then investigated for function. These studies frequently use biochemical techniques that can be imprecise and cumbersome. Mass spectrometry (MS)-based tools are becoming important not only in precisely determining the identity of a NP or quantifying a compound with a known sequence, but also in studies where identity and putative function can be determined simultaneously. Tools based on MS and tandem MS (MS/MS) have been developed, both with isotope labeling strategies and label-free methods, that allow accurate quantitation of NP changes associated with behavior or physiological manipulation, concurrent with identification of sequence. MS and MS/MS have also been implemented with sampling methods that incorporate temporal or spatial information while determining functional role of a NP, such as microdialysis (MD) and imaging mass spectrometry (IMS). These advances in MS and sampling techniques allow investigation of a particular biological phenomenon to guide studies aimed to identify and characterize NPs. Permitting function to drive identification of relevant compounds allows for a broader understanding of the molecular underpinnings of these events. The NPs thus identified can then be validated with more conventional techniques, and successive iterations of identification and function determination will provide rich information about these compounds. This function-driven discovery of NPs using MS-based techniques is an important new approach for their study.
神经肽（NP）的研究存在一些独特的挑战，无论是在确定其分子结构还是功能方面。传统研究遵循一种模式，即发现并鉴定新的神经肽，然后研究其功能。这些研究经常使用可能不精确且繁琐的生化技术。基于质谱（MS）的工具不仅在精确确定神经肽的身份或定量已知序列的化合物方面变得越来越重要，而且在可以同时确定身份和推定功能的研究中也很重要。已经开发了基于MS和串联质谱（MS/MS）的工具，包括同位素标记策略和无标记方法，这些方法可以在确定序列的同时，准确量化与行为或生理操作相关的神经肽变化。MS和MS/MS还与结合时间或空间信息的采样方法一起应用，同时确定神经肽的功能作用，如微透析（MD）和成像质谱（IMS）。MS和采样技术的这些进展使得能够研究特定的生物学现象，以指导旨在识别和表征神经肽的研究。允许功能驱动相关化合物的鉴定有助于更广泛地理解这些事件的分子基础。然后可以用更传统的技术验证由此鉴定出的神经肽，并且鉴定和功能测定的连续迭代将提供有关这些化合物的丰富信息。这种使用基于MS的技术由功能驱动的神经肽发现是其研究的一种重要新方法。
