Parallel Synthesis Of Anticancer, Antiinflammatory, And Antiviral Agents Derived From L- And D-amino Acids

2008 ◽  
pp. 177-194
Author(s):  
David Fairlie ◽  
Robert Reid
Keyword(s):  
Amino Acids ◽  
Antiviral Agents ◽  
Parallel Synthesis

scholarly journals Amino Acids 1055 to 1192 in the S2 Region of Severe Acute Respiratory Syndrome Coronavirus S Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents

2005 ◽  
Vol 79 (6) ◽  
pp. 3289-3296 ◽  
Author(s):  
Choong-Tat Keng ◽  
Aihua Zhang ◽  
Shuo Shen ◽  
Kuo-Ming Lip ◽  
Burtram C. Fielding ◽  
...  
Keyword(s):  
Amino Acids ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Antiviral Agents ◽  
Host Cells ◽  
Heptad Repeat ◽  
Antigenic Determinants ◽  
Amino Acid Residues ◽  
S Protein

ABSTRACT The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) interacts with cellular receptors to mediate membrane fusion, allowing viral entry into host cells; hence it is recognized as the primary target of neutralizing antibodies, and therefore knowledge of antigenic determinants that can elicit neutralizing antibodies could be beneficial for the development of a protective vaccine. Here, we expressed five different fragments of S, covering the entire ectodomain (amino acids 48 to 1192), as glutathione S-transferase fusion proteins in Escherichia coli and used the purified proteins to raise antibodies in rabbits. By Western blot analysis and immunoprecipitation experiments, we showed that all the antibodies are specific and highly sensitive to both the native and denatured forms of the full-length S protein expressed in virus-infected cells and transfected cells, respectively. Indirect immunofluorescence performed on fixed but unpermeabilized cells showed that these antibodies can recognize the mature form of S on the cell surface. All the antibodies were also able to detect the maturation of the 200-kDa form of S to the 210-kDa form by pulse-chase experiments. When the antibodies were tested for their ability to inhibit SARS-CoV propagation in Vero E6 culture, it was found that the anti-SΔ10 antibody, which was targeted to amino acid residues 1029 to 1192 of S, which include heptad repeat 2, has strong neutralizing activities, suggesting that this region of S carries neutralizing epitopes and is very important for virus entry into cells.

Parallel synthesis of homochiral β-amino acids

2007 ◽  
Vol 18 (13) ◽  
pp. 1554-1566 ◽  
Author(s):  
Stephen G. Davies ◽  
Andrew W. Mulvaney ◽  
Angela J. Russell ◽  
Andrew D. Smith
Keyword(s):  
Amino Acids ◽  
Parallel Synthesis

scholarly journals Combining Flavin Photocatalysis with Parallel Synthesis: A General Platform to Optimize Peptides with Non-Proteinogenic Amino Acids

2021 ◽  
Author(s):  
Jacob Immel ◽  
Maheshwerreddy Chilamari ◽  
Steven Bloom
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Structure Activity Relationship ◽  
Parallel Synthesis ◽  
Activity Relationship ◽  
Peptide Drugs ◽  
Sar Studies ◽  
Structure Activity

Most peptide drugs contain non-proteinogenic amino acids (NPAAs), born out through extensive structure-activity relationship (SAR) studies using solid-phase peptide synthesis (SPPS). Synthetically laborious and expensive to manufacture, NPAAs also can...

Parallel Synthesis of Homochiral β-Amino Acids.

ChemInform ◽  
2007 ◽  
Vol 38 (51) ◽  
Author(s):  
Stephen G. Davies ◽  
Andrew W. Mulvaney ◽  
Angela J. Russell ◽  
Andrew D. Smith
Keyword(s):  
Amino Acids ◽  
Parallel Synthesis

scholarly journals Specificity of human rhinovirus 2Apro is determined by combined spatial properties of four cleavage site residues

2013 ◽  
Vol 94 (7) ◽  
pp. 1535-1546 ◽  
Author(s):  
David Neubauer ◽  
Martina Aumayr ◽  
Irene Gösler ◽  
Tim Skern
Keyword(s):  
Amino Acids ◽  
Substrate Specificity ◽  
Cleavage Site ◽  
Antiviral Agents ◽  
Genetic Group ◽  
Human Rhinovirus ◽  
C Terminus ◽  
Group B

The 2A proteinase (2Apro) of human rhinoviruses cleaves the virally encoded polyprotein between the C terminus of VP1 and its own N terminus. Poor understanding of the 2Apro substrate specificity of this enzyme has hampered progress in developing inhibitors that may serve as antiviral agents. We show here that the 2Apro of human rhinovirus (HRV) 1A and 2 (rhinoviruses from genetic group A) cannot self-process at the HRV14 (a genetic group B rhinovirus) cleavage site. When the amino acids in the cleavage site of HRV2 2Apro (Ile-Ile-Thr-Thr-Ala*Gly-Pro-Ser-Asp) were singly or doubly replaced with the corresponding HRV14 residues (Asp-Ile-Lys-Ser-Tyr*Gly-Leu-Gly-Pro) at positions from P3 to P2′, HRV1A and HRV2 2Apro cleavage took place at WT levels. However, when three or more positions of the HRV1A or 2 2Apro were substituted (e.g. at P2, P1 and P2′), cleavage in vitro was essentially eliminated. Introduction of the full HRV14 cleavage site into a full-length clone of the HRV1A and transfection of HeLa cells with a transcribed RNA did not give rise to viable virus. In contrast, revertant viruses bearing cysteine at the P1 position or proline at P2′ were obtained when an RNA bearing the three inhibitory amino acids was transfected. Reversions in the enzyme affecting substrate specificity were not found in any of the in vivo experiments. Modelling of oligopeptide substrates onto the structure of HRV2 2Apro revealed no appreciable differences in residues of HRV2 and HRV14 in the respective substrate binding sites, suggesting that the overall shape of the substrate is important in determining binding efficiency.

Synthesis of Novel Oxazolyl Amino Acids and Their Use in the Parallel Synthesis of Disubstituted Oxazole Libraries

Synthesis ◽  
2018 ◽  
Vol 50 (07) ◽  
pp. 1546-1554 ◽  
Author(s):  
Adel Nefzi ◽  
Siva Murru ◽  
Ramesh Bista
Keyword(s):  
Amino Acids ◽  
Methyl Ester ◽  
Small Molecules ◽  
High Purity ◽  
Solid Phase ◽  
Building Blocks ◽  
Parallel Synthesis ◽  
General Nature

Novel chiral oxazolyl alanine and homologues are synthesized and utilized as building blocks for the solid-phase parallel synthesis of novel trifunctional oxazole small molecules in good to excellent overall yields and with high purity. The orthogonal deprotection strategy of oxazolyl amino acids, prepared from serine methyl ester and amino acids such as aspartic and glutamic acids, allows multiple sites of diversification to make a variety of pharmacologically relevant small molecules. The general nature of this approach allows the preparation of a large number of small molecules and peptidomimetics.

scholarly journals Comparison of Structural Architecture of HCV NS3 Genotype 1 versus Pakistani Genotype 3a

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Kaneez Fatima ◽  
Esam Azhar ◽  
Shilu Mathew ◽  
Ghazi Damanhouri ◽  
Ishtiaq Qadri
Keyword(s):  
Amino Acids ◽  
Structural Characterization ◽  
Antiviral Agents ◽  
Interaction Patterns ◽  
Genotype 1 ◽  
Genome Variability ◽  
Structural Architecture ◽  
Genotype 3A

This study described the structural characterization of Pakistani HCV NS3 GT3a in parallel with genotypes 1a and 1b NS3. We investigated the role of amino acids and their interaction patterns in different HCV genotypes by crystallographic modeling. Different softwares were used to study the interaction pattern, for example, CLCBIO sequence viewer, MODELLER, NMRCLUST, ERRAT score, and MODELLER. Sixty models were produced and clustered into groups and the best model of PK-NCVI/Pk3a NS3 was selected and studied further to check the variability with other HCV NS3 genotypes. This study will help in future to understand the structural architecture of HCV genome variability and to further define the conserved targets for antiviral agents.

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