Author
H S Cheung
Bio: H S Cheung is an academic researcher from Princeton University. The author has contributed to research in topics: Angiotensin-converting enzyme & Angiotensin II. The author has an hindex of 7, co-authored 8 publications receiving 1887 citations.
Papers
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896 citations
TL;DR: Results suggest that selective binding of the COOH-terminal dipeptide residue is an impor tan t dete rminant of both the substrate specificity of angiotensin-converting enzyme and the degree of rate stimulation by chloride ion, and that the nature of this selective binding can be further clarified by studying competitive inhibition of dpeptides of vary ing structure.
721 citations
TL;DR: A hypothetical model of the mechanism of binding of substrates to its active site of angiotensin-converting enzyme is developed and more potent inhibitors of the enzyme that were shown to be orally active in rats are synthesized.
86 citations
TL;DR: In this paper, weis mit Analogen der im Gifte vonBothrops jararaca gefundenen Peptide, dass die Inhihibition des Angiotensins "converting enzyme" von zwei eindeutigen Teilsequenzen dieser Peptides abhangig ist.
Abstract: Nachweis mit Analogen der im Gifte vonBothrops jararaca gefundenen Peptide, dass die Inhihibition des Angiotensins «converting enzyme» von zwei eindeutigen Teilsequenzen dieser Peptide abhangig ist. Die hohe spezifische kompetitive Inhibition, hervorgerufen durch die Peptide vonBothrops jararaca, wird der Bindung ihrer Tripeptidreste vom Carboxyterminus mit dem aktiven Zentrum des Enzyms zugeschrieben, die in gleicher Weise wie die Peptidsubstrate mit dem Enzym gebunden werden. Die Wirksamkeit der Giftpeptide hangt von der Bindung eines zweiten Teiles der Peptide mit dem Enzym ab.
85 citations
TL;DR: The hypothetical working model of the active site of angiotensin-converting enzyme used to develop captopril continues to provide a firm basis for development of new types of specific inhibitors of this biologically important enzyme.
Abstract: Captopril is a remarkably effective new antihypertensive drug designed and developed as a potent and specific inhibitor of angiotensin-converting enzyme, a zinc metallopeptidase that participates in the synthesis of a hypertensive peptide, angiotensin II, and in the degradation of a hypotensive peptide, bradykinin. Earlier studies with a snake venom peptide (teprotride or SQ 20881) that could be administered only by injection demonstrated that specific inhibitors of angiotensin-converting enzyme could be highly effective as antihypertensive drugs, and helped to clarify the specificity and mechanism of action of the enzyme. A hypothetical model of the active center of angiotensin-converting enzyme based on its presumed analogy to the well characterized zinc metallopeptidase carboxypeptidase A was used to guide logical sequential improvements of a weakly active prototype inhibitor that led eventually to the highly optimized structure of captopril. The hypothetical working model of the active site of angiotensin-converting enzyme used to develop captopril continues to provide a firm basis for development of new types of specific inhibitors of this biologically important enzyme.
55 citations
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TL;DR: A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled a new class of potent and specific inhibitors, carboxyalkanoyl and mercaptoalkanoysl derivatives of proline, to be designed.
Abstract: A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.
1,759 citations
TL;DR: The present work is a compilation of recent information on collagen and gelatin extraction from new sources, as well as new processing conditions and potential novel or improved applications, many of which are largely based on induced cross-linking, blending with other biopolymers or enzymatic hydrolysis.
1,496 citations
1,394 citations
Book•
15 Sep 2011
TL;DR: This paper examined the relationship between firm size and research productivity in the pharmaceutical industry and found that larger research efforts are more productive, not only because they enjoy economies of scale, but also because they realize economies of scope by sustaining diverse portfolios of research projects that capture internal and external knowledge spillovers.
Abstract: We examine the relationship between firm size and research productivity in the pharmaceutical industry. Using detailed internal firm data, we find that larger research efforts are more productive, not only because they enjoy economies of scale, but also because they realize economies of scope by sustaining diverse portfolios of research projects that capture internal and external knowledge spillovers. In pharmaceuticals, economies of scope in research are important in shaping the boundaries of the firm, and it may be worth tolerating the static efficiency loss attributable to the market power of large firms in exchange for their superior innovative performance.
995 citations
896 citations