Smith-White M A, Potter E K
Prince of Wales Medical Research Institute, Randwick, Sydney, Australia.
Neuropeptides. 1999 Dec;33(6):526-33. doi: 10.1054/npep.1999.0774.
Neuropeptide Y (NPY) and a C-terminal analog of NPY, N acetyl [Leu(28,31)] NPY 24-36, act at NPY Y(2) receptors to potently inhibit cardiac vagal activity. The C-terminal analog is equipotent as NPY in inhibiting cardiac vagal activity but does not retain any pressor or Y(1) activity. This study investigates the importance of each amino acid in the 13 residue analog for functional activity by systematically substituting each residue with L-alanine. The inhibitory effect on cardiac vagal action decreased with substitution at residues 25,26,28,29 and 31. No decrease in activity was observed with alanine substitution at residues 24, 27 or 30. Residues 32 and 34 retained activity only at high doses, while residues 33, 35 and 36 were not active following alanine substitution. The difference in potency of the effective analogs suggests secondary structure of the peptide is as important for activity as retaining key amino acids.
神经肽Y（NPY）及其C端类似物N-乙酰基[Leu(28,31)]NPY 24-36作用于NPY Y(2)受体，可有效抑制心脏迷走神经活动。该C端类似物在抑制心脏迷走神经活动方面与NPY等效，但不保留任何升压或Y(1)活性。本研究通过将13个残基类似物中的每个残基系统地替换为L-丙氨酸，研究了每个氨基酸对功能活性的重要性。在第25、26、28、29和31位残基进行替换时，对心脏迷走神经作用的抑制效果降低。在第24、27或30位残基用丙氨酸替换时，未观察到活性降低。第32和34位残基仅在高剂量时保留活性，而在丙氨酸替换后，第33、35和36位残基无活性。有效类似物效力的差异表明，肽的二级结构对活性的重要性与保留关键氨基酸一样。
