Welcome to the page of my science!

Welcome to the page of my science!

(欢迎来到我的科学主页, 下半部分是相应中文内容)

By Tianxin Wang 王天欣

These are ideas I had many years ago in the 1990s and one of them had been proved by another group later in publication after I proposed to them. Although I may not be able to try them and publish them by myself, I would like to share them here:

Below are the two theories/methods I proposed/invented:

1) A universal method to develop novel enzymes and catalysts: Selection by reaction PDF format

2) The Decorated RNA Supermolecular World and A Method to Develop Novel Ligands and Catalysts PDF format

which potentially have significance in many fields of life science and can be used in applications including biotechnology, medicine, pharmaceuticals and chemistry.

The RNA World theory [1] assumes that the chemical process leading to the appearance of life was carried out by RNA. In recent years, continuous discoveries of catalytic RNA and DNA [2] by the in vitro selection method greatly support this theory. However, these catalytic RNA’s functions are still very limited and cannot explain the transition from RNA world to today’s Protein world. In the early 1990s I proposed a new theory for the origin of life. Based on this theory, instead of a single-strained “pure” RNA, the RNA (DNA) supermolecular system consisting of several partially complementary RNA (or DNA) strands, among which, some are covalently modified by other molecules (such as amino acid and peptide) were the key bio molecules in the primitive soup. This type of supermolecular systems is also very useful in developing novel ligands and catalysts.

1) Walter Gilbert: Nature, 1986, Vol.319, 618

2) Kandasamy Sakthivel, Carlos F. Barbas: Angew. Chem .Int. Ed. 1998 (37), 2872; Adam Roth, Ronald R. Breaker: Proc. Natl. Acad. Sci. USA 1998 (95) 6027-6031; T.M.Tarasow, S.L.Tarasow, B.E.Eaton: Nature, 1997,389,54-57

Controlling and accelerating reaction like enzymes is always the central topic of chemistry. In 1986, Lerner R’s group [1] and Schultz PG’s group [2] proposed the catalytic antibody strategy (abzyme), which allow chemist to develop novel artificial enzymes for many reactions, which was a breakthrough in this field. However, catalytic antibody strategy has its intrinsic limitations, which greatly hindered its industrial application, till now only one catalytic antibody has been used in small industrial scale (and in fact even this one is developed using reactive hapten [3], an ingenious improvement on catalytic by Janda KD instead of using transitional state mimics). I designed a new strategy: Selection by Reaction and proposed this strategy to the two inventors of catalytic antibody in 1997 and received the reply from Dr. K. D. Janda. Although no reply from Schultz PG, several months later without acknowledging my original proposal to him his group published a paper using a known enzyme as model proved the feasibility of this strategy and suggested that it could be used for protein functional cloning in proteomic study [4]. This method overcomes the limitation of catalytic antibody and is showing [5, 6] potential in life science and chemistry.

1) Tramontano A, Janda KD, Lerner RA. Proc Natl Acad Sci U S A 1986 September;83(18):6736-40; Science 1986 Dec 19;234(4783):1566-70

2) Pollack SJ, Jacobs JW, Schultz PG; Science 1986 December 19; 234 (4783):1570-3

3) Janda KD, Lo LC, Lo CH, Sim MM, Wang R, Wong CH, Lerner RA. Science 1997 February 14;275(5302):945-8

4) Henrik Pedersen , Holder S, Sutherlin DP,Schwitter U,King DS, Schultz PG. Proc. Natl. Acad. Sci. USA. 1998 September 1; 95 (18): 10523–10528

5) Liu, D.R.; Schultz, P.G. Angew. Chem. Int. Engl. Ed., 38:36-54, 1999.

6) Xia G, Chen L, Sera T, Fa M, Schultz PG, Romesberg FE. Proc Natl Acad Sci U S A 2002 May 14;99(10):6597-602

以下是我于上世纪90年代在世界上率先提出和发明的两项理论和技术：

1) 杂和的 RNA超分子系统: 一种生命起源的新解释, 以及发展新型配体和催化剂的新方法 PDF 文件

2) 从反应本身寻找: 发展新型催化功能 (蛋白基和聚合物基) 以及酶功能定位的普适通用方法 PDF 文件

它们有潜力为生命科技的多个领域提供有力的工具和理论; 并在医药，化工，生物，环境等各方面具有潜在实用价值。

生命起源始终是人类不倦探索的问题. RNA世界理论[1] 认为 RNA 在导致生命起源的化学过程中起了主导作用, 既是功能性分子又是遗传性分子. 近些年来, 多种催化性RNA和DNA 被应用试管进化方法不断发现. 这些催化性核酸的发现[2]进一步支持了RNA世界理论. 但这些催化性核酸的功能和效率十分有限, 也无法解释RNA世界如何进化为如今的蛋白质世界.

因此我于90年代初提出了杂和的RNA超分子系统理论可以作为生命起源的新解释. 依照这个理论, 在生命发展的初期阶段, RNA超分子系统是最重要的生物活性物质. RNA超分子系统是由几条部分互补的RNA组成的超分子自组装体系, 其中的某些RNA或DNA是被其它非核酸物质如氨基酸和多肽等共价修饰的. 这个假说统一了RNA世界理论和蛋白质世界理论, 更重要的是这个理论也同时提供了发展新型配体和催化剂的新方法, 从而有望具有广泛的实用意义和价值.

1) Walter Gilbert: Nature, 1986, Vol.319, 618

催化和控制反应是化学最根本的课题.能够针对各种反应随意发展象酶那样高效主动地人工催化剂一直是化学家的梦想. 1986 年, Lerner RA的研究小组[1] 和Schultz PG的研究小组[2] 发明了催化抗体的方法; 使得人们首次可以针对某些反应主动发展类似于酶的蛋白催化剂, 是这一领域的巨大突破. 但催化抗体的方法也存在一系列根本的缺欠, 从而限制了其实际应用. 到目前为止只有一种在小规模工业合成上得到了应用 (实际上这种催化抗体也并非是用反应过渡态模拟物来诱导抗体制备的, 而是用Janda KD对催化抗体的巧妙改进: 活性抗原来制备的 [3]).

1997年我提出了从反应本身寻找发展新型催化功能 (蛋白基和聚合物基)的普适通用方法并向催化抗体的发明者们提出了这个建议，并得到了Janda 博士的回复。虽然没有得到Schultz PG的回应, 数月后他的小组发表了论文，应用一个已知酶作为模型证实了该方法的可行性，并进一步提出该方法可以在蛋白组研究中寻找基因组功能的对应物 [4], 但遗憾的是该论文并未提及之前我对他们提供该建议。该方法克服了催化抗体的根本的缺欠; 现在越来越多的研究 [5,6] 开始应用这个方法, 逐渐显示出其应用价值.

1) Tramontano A, Janda KD, Lerner RA. Proc Natl Acad Sci U S A 1986 September;83(18):6736-40; Science 1986 Dec 19;234(4783):1566-70

2) Pollack SJ, Jacobs JW, Schultz PG; Science 1986 December 19; 234 (4783):1570-3

3) Janda KD, Lo LC, Lo CH, Sim MM, Wang R, Wong CH, Lerner RA. Science 1997 February 14;275(5302):945-8

4) Henrik Pedersen , Holder S, Sutherlin DP,Schwitter U,King DS, Schultz PG. Proc. Natl. Acad. Sci. USA. 1998 September 1; 95 (18): 10523–10528

5) Liu, D.R.; Schultz, P.G. Angew. Chem. Int. Engl. Ed., 38:36-54, 1999.

6) Xia G, Chen L, Sera T, Fa M, Schultz PG, Romesberg FE. Proc Natl Acad Sci U S A 2002 May 14;99(10):6597-602

Welcome to the page of my science!

(欢迎来到我的科学主页)