Proenkephalin Processing

化学信使分子，包括激素和神经递质，介导所有生物体的邻近和遥远部分之间的交流。这些信使中的许多首先以非活性前体形式产生，在它们对细胞和组织发挥生物作用之前需要激活。许多前体分子通过这一激活过程产生一种以上的活性信使。这项研究将检查生物体在处理这些前体时使用的规则。一个模型前体分子，前脑啡肽，将被研究。proenkephalin的结构将使用重组DNA技术进行修饰，以揭示分子的哪些部分是通常的加工位点，以及分子的各种结构特征对加工的影响。同样使用同样的技术，将尝试构建新型的前体，这些前体将产生单个活跃的信使，而无需经过大量的过程。这种“最小的”前体可能对基因治疗中特定激素或神经递质的递送有用。

Chemical messenger molecules, including hormones and neurotransmitters, mediate communication between adjacent and distant parts of all organisms. Many of these messengers are first produced in inactive precursor forms that requireactivation before they can exert their biological action on cells and tissues. Many precursor molecules give rise to more than one type of active messenger through this activation process. This study will examine what rules the organisms uses in the processing of these precursors. A model precursor molecule, proenkephalin, will be studied. The structure of proenkephalin will be modified using recombinant DNA technology to reveal what parts of the molecule are the usual sites for processing and what influences various structural features of the molecule have on processing. Also using this same technology, an attempt will be made to construct new types of precursors that will generate single active messengers without having to go through extensive procession. Such "minimal" precursors may be useful for delivery of specific hormones or neurotransmitters in gene therapy.