2018/10/27 Saturday Bradykinin Potentiating Factor,BPF r8 Sergio H.Fe 1934-2016 Teprotide替普罗肽 ,随后将其取名为“缓表肚 但是这种 期，儿分钟 发现地运精暖的作用 Ligand-based Drug Design Rational Drug Design 施责宝捡了个宝 Bristol-Myers Squibh John Robert Vane and Miguel Ondetti Cushman在《生物化学杂志》上看到Byersz和Nolfenden2发表的一篇关 子新型数肤酶A抑制剂苄基琉珀酸的文章，这篇文章使Cushman看到 ACE抑制剂研发的曙光.子是他清来Ode一块讨论。试用从活性结构 相对明确的獭基肤酶及其抑制剂中寻找交口。 6
2018/10/27 Saturday 6 1933年，刚毕业的Maurício Oscar da Rocha e Silva，曾目睹了一位被巴西蝮蛇 咬伤的患者不治而死的全过程。1948年他从蛇毒中成功提取了一个具有多肽结构的 特殊物质，并证实该多肽可导致血管扩张，随后将其取名为“缓激肽”，但是这种 物质在血液里的半衰期很短，几分钟就完全失效了，因此没有太大的实用价值。 1965年，Sérgio Henrique Ferreira (Maurício Oscar da Rocha e Silva的博士生) 发现蛇毒本身还具有增强缓激肽的作用. Bradykinin Potentiating Factor, BPF Maurício O. Rocha e Silva (1910-1983) Sérgio H. Ferreira (1934 –2016) Bradykinin 缓激肽 Teprotide 替普罗肽 Ligand-based Drug Design Cushman在《生物化学杂志》上看到Byers和Wolfenden发表的一篇关 于新型羧肽酶Ａ抑制剂苄基琥珀酸的文章，这篇文章使Cushman看到 ACE抑制剂研发的曙光，于是他请来Ondetti一块讨论，试图从活性结构 相对明确的羧基肽酶及其抑制剂中寻找突破口。 Rational Drug Design John Robert Vane Dave Cushman and Miguel Ondetti 施贵宝 捡了个宝 Bristol-Myers Squibb
2018/10/27 Saturday Lead compounds from the natural world Captopril-1999 Albert Lasker Clinical Medical Research Award Venoms and toxins 的 David Cushman and miguel ond HS. 心 OH Captopril (anti-hy pertensive) 卡托普利，DA1982 Serendipity Finding "Chance favors the prepared mind" Alexander Fleming discovered penicillin in 198 but The first real breakthrough in the field of anti-infectives was the discovery of the B-lactam antibiotics such as penicillin G.Fleming received Nobel Prize in 1945. H.W.Florey goterud Penicillin in put it into cinic use. 7
2018/10/27 Saturday 7 Lead compounds from the natural world Captopril (anti-hypertensive) Venoms and toxins David Cushman and Miguel Ondetti Captopril ---1999 Albert Lasker Clinical Medical Research Award 卡托普利, FDA 1982 74 C C O NH N S H H H COOH H H O The first real breakthrough in the field of anti-infectives was the discovery of the -lactam antibiotics such as penicillin G. Fleming received Nobel Prize in 1945. H. W. Florey got crud Penicillin in 1940 and put it into clinic use. Alexander Fleming discovered penicillin in 1928 but 1943 in clinic. Serendipity Finding “Chance favors the prepared mind
2018/10/27 Saturday Dorothy Hodgkin determined the chemical structure of penicillin 魔舞更什公紧 Synthesizing Penicillin 0-2002 在解折青塞素的结(194) 1915-99ha nade1961 into After nine years of hard work at the Massachusetts Institute of g pen 8
2018/10/27 Saturday 8 75 Dorothy Hodgkin determined the chemical structure of penicillin 牛津大学科学史博物馆中摆 放着霍奇金发现青霉素分子 结构的示意模型，黑色线圈 表示电子云，从线圈的密度 能推断出是什么原子 Molecular model of penicillin by Dorothy Hodgkin, c. 1945 76 Synthesizing Penicillin . John Clark Sheehan (1915 –1992) After nine years of hard work at the Massachusetts Institute of Technology (M.I.T.), he became the first to discover a practical method for synthesizing penicillin V in 1957. Ampicillin, a commonly used semi-synthetic penicillin that is taken orally rather than by injection, was discovered in 1958 and came into commercial use in 1961. Edward Abraham, Wilson Baker (1900-2002), Erns Chain, Robert Robinson 在解析青霉素的结（1944）
2018/10/27 Saturday Dorothy C.Hodgkin And Vitamin B12 a. “ First disclosed at a symposium in 1961 then in a publication in 1962 A Molecule You Can't Live Without It-Cholesterol and some sex hormones. 9
2018/10/27 Saturday 9 77 Dorothy C. Hodgkin And Vitamin B12 First disclosed at a symposium in 1961; then in a publication in 1962 A Molecule You Can't Live Without It-Cholesterol Cholesterol plays an essential role in the cell's functioning; it stabilizes cell membrane structures and is the biochemical "parent" of cortisone and some sex hormones
2018/10/27 Saturday Cholesterol and Cardiovascular Disease Regulation of cholesterol synthesis used on the attention to HMG-CoA s the rate- ng enzyme in the 含 Cholesterol Biosynthetic Pathway Elucidated step in bio “o holester 人人人 人人 g69 一 o6dFooraenedtcobdrhwcoea9 0
2018/10/27 Saturday 10 Cholesterol and Cardiovascular Disease 1815 isolated 1950's Biosynthetic pathway elucidated HO H H H H Feodor F. K. Lynen 1964 NP Konrad E. Bloch 1964 NP Michel E. Chevreul This finding focused on the attention to HMG-CoA reductase as the rate-controlling enzyme in the Cholesterol biosynthetic pawthway. Their studies led to the development of statin drugs Regulation of cholesterol synthesis 发现胆固醇合成的 原料—乙酰辅酶A Konrad Emil Bloch (1912-2000) Cholesterol Biosynthetic Pathway Elucidated Feodor Felix Konrad Lynen (1911-1979) Bloch and Feodor Lynen received the Nobel Prize in Physiology or Medicine in 1964 for discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism. Cholesterol Biosynthetic pathway elucidated in 1950. acetyl CoA + acetoacetyl CoA HMG CoA HMG CoA synthase HMG CoA reductase mevalonate mevalonate PP farnesyl PP squalene lanosterol cholesterol HO SCoA O OH O HO OH O OH HO PP O OH PP farnesylated proteins HO H H HO H H H H steroid hormones vitamin D bile acids What inhibiting the rate-limiting step in biosyn. pathway of cholesterol