Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus

提出的研究项目代表了一种使用全化学合成来研究HIV-1 PR酶作用的新方法，HIV-1 PR是艾滋病病毒复制所必需的天冬氨酸蛋白酶。重新设计催化装置将使我们能够研究其作用的分子方面。合成的多肽链将被折叠，并通过核磁共振表征正确的折叠结构，并测定酶活性。可以预期，对HIV-1 PR特性的分子基础将获得重要的新见解。这将是对生物医学研究的重要贡献。

The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folded structure by NMR, and assayed for enzymatic activity. It can be expected that significant new insights into the molecular basis of the properties of the HIV-1 PR will be obtained. This will be an important contribution to biomedical research.