Enantioselective organocatalytic syntheses of α-selenated α- and β-amino acid derivatives

Selenium-containing amino acids are valuable targets but methods for the stereoselective α-selenation of simple amino acid precursors are rare. We herein report the enantioselective electrophilic α-selenation of azlactones (masked α-amino...

Targeting protease nexin-1, a natural anticoagulant serpin, to control bleeding and improve hemostasis in hemophilia

Targeting natural anticoagulant proteins as a means to rebalance the hemostatic system is an emerging trend in the development of innovative therapeutic strategies for hemophilia. These 2 articles develop these concepts in the areas of hemostasis and contact activation. In the study by Aymonnier and colleagues, simple amino acid substitutions converted a serpin elastase inhibitor, α1-antitrypsin (α1AT), into a potent antithrombin, activated protein C inhibitor, or anti-PKa/FXIIa inhibitor. In the study by de Maat and colleagues, redesign of α1AT strongly altered its inhibitory behavior and enables it to be used for the treatment of contact system–mediated thrombosis and inflammation.

Design and characterization of α1-antitrypsin variants for treatment of contact system–driven thromboinflammation

Targeting natural anticoagulant proteins as a means to rebalance the hemostatic system is an emerging trend in the development of innovative therapeutic strategies for hemophilia. These 2 articles develop these concepts in the areas of hemostasis and contact activation. In the study by Aymonnier and colleagues, simple amino acid substitutions converted a serpin elastase inhibitor, α1-antitrypsin (α1AT), into a potent antithrombin, activated protein C inhibitor, or anti-PKa/FXIIa inhibitor. In the study by de Maat and colleagues, redesign of α1AT strongly altered its inhibitory behavior and enables it to be used for the treatment of contact system–mediated thrombosis and inflammation.

SeqStruct: A New Amino Acid Similarity Matrix Based on Sequence Correlations and Structural Contacts Yields Sequence-Structure Congruence

SUMMARYProtein sequence matching does not properly account for some well-known features of protein structures: surface residues being more variable than core residues, the high packing densities in globular proteins, and does not yield good matches of sequences of many proteins known to be close structural relatives. There are now abundant protein sequences and structures to enable major improvements to sequence matching. Here, we utilize structural frameworks to mount the observed correlated sequences to identify the most important correlated parts. The rationale is that protein structures provide the important physical framework for improving sequence matching. Combining the sequence and structure data in this way leads to a simple amino acid substitution matrix that can be readily incorporated into any sequence matching. This enables the incorporation of allosteric information into sequence matching and transforms it effectively from a 1-D to a 3-D procedure. The results from testing in over 3,000 sequence matches demonstrate a 37% gain in sequence similarity and a loss of 26% of the gaps when compared with the use of BLOSUM62. And, importantly there are major gains in the specificity of sequence matching across diverse proteins. Specifically, all known cases where protein structures match but sequences do not match well are resolved.

l-Alanine capping of ZnO nanorods: increased carrier concentration in ZnO/CuI heterojunction diode

ZnO nanorods were capped with a simple amino acid, viz., l-Alanine to increase the carrier concentration and improve the performance of ZnO/CuI heterojunction diodes.