Peptidic α-Ketocarboxylic Acids and Sulfonamides as Inhibitors of Protein Tyrosine Phosphatases

One common approach for designing protein tyrosine phosphatase (PTPase) inhibitors is to incorporate a nonhydrolyzable phosphotyrosine (pTyr) mimic into a peptide substrate for PTPases. This report describes the synthesis of three such nonhydrolyzable pTyr mimics that contain α-ketoacid, α-hydroxyacid, and methylenesulfonamide functional groups in place of the phosphate. These pTyr mimics were incorporated into the peptide sequence Ac-Asp-Ala-Asp-Glu-X-Leu-NH2, where X is the pTyr mimic, and analyzed for activity against the Yersinia PTPase and PTP1B

Total Synthesis of Kopsinine

The use of a powerful intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of an 1,3,4-oxadiazole in the divergent total synthesis of kopsinine (<b>1</b>), featuring an additional unique SmI₂-promoted transannular cyclization reaction for formation of the bicyclo[2.2.2]octane central to its hexacyclic ring system, is detailed

Squaric Acids: A New Motif for Designing Inhibitors of Protein Tyrosine Phosphatases

Protein tyrosine phosphatases (PTPases) are important targets in medicinal chemistry. These enzymes play a role in a number of human diseases, including type II diabetes and infection by Yersinia pestis, the causative agent of bubonic plague. Derivatives of squaric acids such as 2-aryl-1-hydroxycyclobut-1-ene-3,4-diones represent a new class of monoanionic inhibitors for PTPases

Parameters employed in the simulations.

Parameters employed in the simulations.</p

Algorithm flow chart of the proposed transmission model.

<p>The algorithm is based on Yes/No (Y/N) judge model.</p

Throughput of different sub-contents.

<p>This simulation is based on 25%–75% condition.</p

Throughput comparison with the other models.

<p>This comparison is based on 25%–75% condition.</p

Delay of the three transmission models.

<p>This simulation is based on 25%–75% condition.</p

Transmission example.

<p>It is an example based on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0196818#pone.0196818.g001" target="_blank">Fig 1</a> of two-hop transmission from node S to node D via node B as a relay node based on content structured according to DCC.</p

Throughput comparison with the other models.

<p>The simulation is based on two conditions, 25%–75% condition and 10%–90% condition, respectively.</p