Laboratoire Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UMR 7369, Université de Reims, Faculté des Sciences, Reims Cedex 2, France; Groupe de Biophysique Moléculaire, Sorbonne Paris Cité, Université Paris 13, UFR Santé-Médecine-Biologie Humaine, Bobigny, France.
Institut Pasteur, Unité de Chimie des Biomolécules, UMR 3523, Paris Cedex 15, France.
Adv Protein Chem Struct Biol. 2018;112:81-121. doi: 10.1016/bs.apcsb.2018.01.002. Epub 2018 Feb 23.
Primarily known as the inhibitor of growth hormone release, the role of somatostatin in many other inhibiting activities upon binding to its five G-protein-coupled receptors has been elucidated. Because of the short half-life of somatostatin, a number of synthetic analogues were elaborated for this peptide hormone. Herein, after recalling the main somatostatin therapeutic interests, we present the dynamical behavior of somatostatin-14 and its two currently used synthetic cyclic analogues, octreotide and pasireotide. Physical techniques, such as fluorescence, UV-visible absorption, circular dichroism, Raman spectroscopy, surface-enhanced Raman spectroscopy, and transmission electron microscopy, were jointly used in order to get information on the solution structural features, as well as on the anchoring sites of the three peptides on silver colloids. While somatostatin-14 adopts a rather unordered chain within the submillimolar concentration range, its cyclic analogues were revealed to be ordered, i.e., stabilized either in a type-II' β-turn (octreotide) or in a face-to-face γ-turn/type-I β-turn (pasireotide) structure. Nevertheless, a progressive structuring trend was observed in somatostatin-14 upon increasing concentration to the millimolar range. Because of their cationic character, the three peptides have revealed their capability to bind onto negatively charged silver nanoparticles. The high affinity of the peptides toward metallic particles seems to be extremely promising for the elaboration of somatostatin-based functionalized plasmonic nanoparticles that can be used in diagnosis, drug delivery, and therapy.
作为生长抑素释放抑制剂而被主要认识，生长抑素与五个 G 蛋白偶联受体结合后在许多其他抑制活性中的作用已经阐明。由于生长抑素的半衰期短，已经对这种肽激素进行了许多合成类似物的阐述。在此，在回顾主要的生长抑素治疗兴趣之后，我们展示了生长抑素-14 及其两种当前使用的合成环状类似物，奥曲肽和帕瑞肽的动力学行为。物理技术，如荧光、紫外-可见吸收、圆二色性、拉曼光谱、表面增强拉曼光谱和透射电子显微镜，被共同用于获取关于溶液结构特征以及三种肽在银胶上的锚定位点的信息。虽然生长抑素-14 在亚毫摩尔浓度范围内采用相当无序的链，但发现其环状类似物是有序的，即，要么稳定在 II'β-转角（奥曲肽）中，要么稳定在面对面γ-转角/ I 型β-转角（帕瑞肽）结构中。然而，在生长抑素-14 浓度增加到毫摩尔范围时，观察到其结构逐渐形成的趋势。由于它们的阳离子特性，三种肽已显示出与带负电荷的银纳米颗粒结合的能力。肽对金属颗粒的高亲和力似乎对于基于生长抑素的功能化等离子体纳米颗粒的研制非常有前途，这些纳米颗粒可用于诊断、药物输送和治疗。
