Krstenansky J L, Owen T J, Buck S H, Hagaman K A, McLean L R
Merrell Dow Research Institute, Cincinnati, OH 45215.
Proc Natl Acad Sci U S A. 1989 Jun;86(12):4377-81. doi: 10.1073/pnas.86.12.4377.
Porcine neuropeptide Y (pNPY) has been proposed to form an intramolecularly stabilized structure characterized by N- and C-terminal helical regions arranged antiparallel due to a central turn region. Analogs based on this structural model that have the central turn region and various amounts of the helical regions removed, yet retain the N and C termini in a similar spatial orientation were designed. The gap formed by removal of the central residues (residues 8-17 or 7-20) was spanned with a single 8-aminooctanoic acid residue (Aoc) and the structure was further stabilized by the introduction of a disulfide bridge. [D-Cys7,Aoc8-17,Cys20]pNPY and [Cys5,Aoc7-20,D-Cys24]pNPY were synthesized and found to have receptor binding affinities of 2.3 nM and 150 nM, respectively, in mouse brain membranes (pNPY affinity is 3.6 nM in this assay). It is proposed that the central region (residues 7-17) of pNPY serves a structural role in the peptide and is not involved in direct receptor interaction.
猪神经肽Y（pNPY）被认为形成一种分子内稳定结构，其特征是由于中央转折区，N端和C端螺旋区呈反平行排列。基于此结构模型设计了类似物，去除了中央转折区和不同数量的螺旋区，但N端和C端保持相似的空间取向。通过去除中央残基（8 - 17位残基或7 - 20位残基）形成的缺口用单个8 - 氨基辛酸残基（Aoc）填补，并且通过引入二硫键进一步稳定结构。合成了[D - Cys7，Aoc8 - 17，Cys20]pNPY和[Cys5，Aoc7 - 20，D - Cys24]pNPY，发现在小鼠脑膜中它们的受体结合亲和力分别为2.3 nM和150 nM（在此测定中pNPY亲和力为3.6 nM）。有人提出pNPY的中央区域（7 - 17位残基）在肽中起结构作用，不参与直接的受体相互作用。
