Barden J A, Cuthbertson R M, Potter E K
Department of Anatomy and Histology, University of Sydney, NSW, Australia.
Biochim Biophys Acta. 1995 Jul 3;1250(1):83-9. doi: 10.1016/0167-4838(95)00047-x.
Neuropeptide Y analog ANA-NPY or [Leu-17, Gln-19, Ala-20, Ala-23, Leu-28, Leu-31]NPY(13-36)-amide binds to postjunctional or Y1 receptors to raise blood pressure and to prejunctional or Y2 receptors to inhibit neurotransmitter release. ANA-NPY affects Y2 receptors in the same way as intact NPY but exhibits far less potent effects on Y1 receptors. The structure of ANA-NPY was examined using two-dimensional proton nuclear magnetic resonance spectroscopy. Complete assignment of all backbone and side chain hydrogens was accomplished with totally correlated spectroscopy (TOCSY) experiments providing through-bond 1H-1H connectivities, and nuclear Overhauser effect spectroscopy (NOESY), providing the through-space and sequential backbone connectivities. The tertiary solution structure of the peptide was performed using distance geometry and dynamic simulated annealing. ANA-NPY exhibits a helical structure with strong amphipathic character with a bend around Glu-24 indicating that the C-terminal segment 25-35 forms a single alpha-helical motif.
神经肽Y类似物ANA - NPY或[亮氨酸-17、谷氨酰胺-19、丙氨酸-20、丙氨酸-23、亮氨酸-28、亮氨酸-31]NPY(13 - 36)-酰胺与突触后或Y1受体结合以升高血压，与突触前或Y2受体结合以抑制神经递质释放。ANA - NPY对Y2受体的影响与完整的神经肽Y相同，但对Y1受体的作用效力要低得多。使用二维质子核磁共振波谱对ANA - NPY的结构进行了研究。通过全相关谱(TOCSY)实验完成了所有主链和侧链氢原子的完全归属，该实验提供了键间1H - 1H连接信息，同时通过核Overhauser效应谱(NOESY)提供了空间和顺序主链连接信息。利用距离几何和动态模拟退火确定了该肽的三级溶液结构。ANA - NPY呈现出具有强两亲性的螺旋结构，在谷氨酸-24周围有一个弯曲，表明C末端片段25 - 35形成一个单一的α - 螺旋基序。
