Simulation of Protein Function by Synthetic Chemistry

对鱼精蛋白和RNA聚合酶II.1等与DNA结合的蛋白质进行了分子水平化学模拟。鱼精蛋白是一种强碱性蛋白质，以核蛋白形式存在于鱼类成熟精子核中。鱼精蛋白与UNA结合强烈，在遗传信息保护中发挥着重要的功能作用。然而，到目前为止，它们与DNA的结合方式尚不清楚。(1)合成了三种突出或抵消鱼精蛋白分子转角结构部分氨基酸序列特征的多肽。(2)上述三种多肽的构象通过CD和~1H核磁共振进行了研究。研究了它们与DNA的相互作用，如稳定DNA的能力和聚集DNA的能力。(3)在许多鱼精蛋白分子中存在一个独特的序列-SRPV-，该部分被认为是分子中的转弯结构部分。合成了三种含有该序列的多肽，即SRPV、SSRPV和SSSRPV。(4)用CD和1H NMR研究了上述三种多肽的构象，通过上述方法获得了有关鱼精蛋白分子中转角结构部分的构象和作用的信息。RNA聚合酶II分子中存在SPTSPSY重复序列，该部分的作用尚不清楚。合成了聚(SPTSPSY)作为这一部分的模型。ExacL构象研究和与DNA的相互作用目前正在进行中。

Simulation of protein function by synLheLic chemistry was carried out for DNA-binding proteins such as protamine and RNA polymerase II.1. Protamines are strongly basic proteins which exist as nucleoprotamines in mature sperm nuclei of fish. Protamines bind strongly to UNA, and play an important functional role in protection of genetic information. however, their DNA-binding mode is unclear so far.(1)Three kinds of peptides, which emphasized or canceled out the characteristics of the amino acid sequence of turn structure portion in protamine molecules, were synthesized.(2)Conformation of the above, -three peptides were investigated by CD and ^1H NMR. Their interaction with DNA such as DNA-stabilizing ability and DNA-aggregating ability was also investigated.(3)An unique sequence, -SRPV-, exists very coservalively in many protamine molecules, and this part is estimated as turn structure portion in the molecule. Three peptide containing this sequence, i. e. SRPV, SSRPV and SSSRPV, were synthesized.(4)Conformation of the above three peptides were investigated by CD and ^1H NMR.By the above mentioned approaches, some informations about the conformation and role of the turn structure portion in the protamine molecule were obtained.2. A repeated sequence of SPTSPSY exists in RNA polymerase II molecule, and the role of this part is unknown. Poly(SPTSPSY)was synthesized as a model for this part. ExacL conformational investigation and interaction with DNA are now in progress.