Faculty Opinions recommendation of Design and synthesis of novel lactate dehydrogenase A inhibitors by fragment-based lead generation.

2012 ◽  
Author(s):  
Celerino Abad-Zapatero
Keyword(s):  
Lactate Dehydrogenase ◽  
Design And Synthesis ◽  
Lead Generation

Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation

2012 ◽  
Vol 55 (7) ◽  
pp. 3285-3306 ◽  
Author(s):  
Richard A. Ward ◽  
Claire Brassington ◽  
Alexander L. Breeze ◽  
Alessandro Caputo ◽  
Susan Critchlow ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Design And Synthesis ◽  
Lead Generation

Design and synthesis of new enzymes based on the lactate dehydrogenase framework

1991 ◽  
Vol 332 (1263) ◽  
pp. 177-184 ◽  
Keyword(s):  
Crystal Structure ◽  
Lactate Dehydrogenase ◽  
Malate Dehydrogenase ◽  
Functional Groups ◽  
Maximum Rate ◽  
Chemical Probes ◽  
Protein Surface ◽  
Design And Synthesis ◽  
Tryptophan Residues ◽  
Lactate Dehydrogenases

Analysis of the mechanism and structure of lactate dehydrogenases is summarized in a map of the catalytic pathway. Chemical probes, single tryptophan residues inserted at specific sites and a crystal structure reveal slow movements of the protein framework that discriminate between closely related small substrates. Only small and correctly charged substrates allow the protein to engulf the substrate in an internal vacuole that is isolated from solvent protons, in which water is frozen and hydride transfer is rapid. The closed vacuole is very sensitive to the size and charge of the substrate and provides discrimination between small substrates that otherwise have too few functional groups to be distinguished at a solvated protein surface. This model was tested against its ability to successfully predict the design and synthesis of new enzymes such as L-hydroxyisocaproate dehydrogenase and fully active malate dehydrogenase. Solvent friction limits the rate of forming the vacuole and thus the maximum rate of catalysis.

Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches

2017 ◽  
Vol 17 (9) ◽  
pp. 1096-1114 ◽  
Author(s):  
Azizeh Abdolmaleki ◽  
Jahan B. Ghasemi
Keyword(s):  
Drug Discovery ◽  
Structural Biology ◽  
Design And Synthesis ◽  
Hybrid Compounds ◽  
Target Drug ◽  
Hybrid Molecules ◽  
Lead Generation ◽  
Multiple Ligands ◽  
New Compounds ◽  
Screening Approaches

Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group’s participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included.

Prostatic Acid Phosphatase (PAP) Differentiated Ultracytochemically from Lysosomal Acid Phosphate in the Rat with a PAP/Specific Substrate, Phosphorylcholine

1975 ◽  
Vol 33 ◽  
pp. 450-451
Author(s):  
W. Allen Shannon ◽  
José A. Serrano ◽  
Hannah L. Wasserkrug ◽  
Anna A. Serrano ◽  
Arnold M. Seligman
Keyword(s):  
Acid Phosphatase ◽  
Phosphate Buffer ◽  
Prostatic Carcinoma ◽  
Prostatic Acid Phosphatase ◽  
Chemotherapeutic Agents ◽  
Specific Substrate ◽  
Acid Phosphate ◽  
Lysosomal Acid ◽  
Design And Synthesis ◽  
New Chemotherapeutic Agents

During the design and synthesis of new chemotherapeutic agents for prostatic carcinoma based on phosphorylated agents which might be enzyme-activated to cytotoxicity, phosphorylcholine, [(CH3)3+NCH2CH2OPO3Ca]Cl-, has been indicated to be a very specific substrate for prostatic acid phosphatase (PAP). This phenomenon has led to the development of specific histochemical and ultracytochemical methods for PAP using modifications of the Gomori lead method for acid phosphatase. Comparative histochemical results in prostate and kidney of the rat have been published earlier with phosphorylcholine (PC) and β-glycerophosphate (βGP). We now report the ultracytochemical results.Minced tissues were fixed in 3% glutaraldehyde-0.1 M phosphate buffered (pH 7.4) for 1.5 hr and rinsed overnight in several changes of 0.05 M phosphate buffer (pH 7.0) containing 7.5% sucrose. Tissues were incubated 30 min to 2 hr in Gomori acid phosphatase medium (2) containing 0.1 M substrate, either PC or βGP.

Tailoring microstructures of materials through biomimetics

1993 ◽  
Vol 51 ◽  
pp. 500-501
Author(s):  
Mehmet Sarikaya ◽  
Ilhan A. Aksay
Keyword(s):  
Chemical Properties ◽  
Design And Synthesis ◽  
Structure Sensitive ◽  
Macro Scale ◽  
Methods Of Synthesis ◽  
Successive Level ◽  
Engineering Materials ◽  
Physical And Chemical ◽  
And Chemical Properties ◽  
Synthesis Of Materials

Biomimetics involves investigation of structure, function, and methods of synthesis of biological composite materials. The goal is to apply this information to the design and synthesis of materials for engineering applications.Properties of engineering materials are structure sensitive through the whole spectrum of dimensions from nanometer to macro scale. The goal in designing and processing of technological materials, therefore, is to control microstructural evolution at each of these dimensions so as to achieve predictable physical and chemical properties. Control at each successive level of dimension, however, is a major challenge as is the retention of integrity between successive levels. Engineering materials are rarely fabricated to achieve more than a few of the desired properties and the synthesis techniques usually involve high temperature or low pressure conditions that are energy inefficient and environmentally damaging.In contrast to human-made materials, organisms synthesize composites whose intricate structures are more controlled at each scale and hierarchical order.

Serum Lactate Dehydrogenase Isoenzyme 1 and Relapse in Patients with Nonseminomatous Testicular Germ Cell Tumors Clinical Stage I

2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Germ Cell ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Serum Lactate ◽  
Stage I ◽  
Serum Lactate Dehydrogenase ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Dehydrogenase Isoenzyme

Design and synthesis of azaisoflavones

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
B Kang ◽  
YJ Jung ◽  
R Jeon
Keyword(s):  
Design And Synthesis
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