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Isopeptide bond formation mediated by δ-selenolysine for chemical ubiquitination

1 Introduction

Protein ubiquitination is a major post-translational modification in Eukaryotes and is involved in nearly all biological processes, i.e., protein degradation, DNA repair, and cell signaling. Hence, unraveling its precise role in health and disease is important (Chaugule and Walden, ; Swatek and Komander, ). Ubiquitin (Ub) is a mer protein found in almost all Eukaryotes. In protein ubiquitination, the C-terminal carboxylate of Ub is attached to the µ-amino group of the lysine residue in the acceptor protein through an isopeptide bond. Ub can form homopolymers, heteropolymers, and branched polymers through its seven Lys residues and one N-terminal Met. This structural diversity allows the formation of the Ub code (Komander and Rape, ; Swatek and Komander, ).

To gain precise insights into the complex Ub codes formed by diverse polyUb chains, researchers frequently employ chemical probes with polyUb chains having a defined linkage attached to a defined position of the acceptor protein (Mulder et al., ). Certain polyUb chains with defined linkage and length can be prepared using specific E2 or E3 enzymes. However, this method has some limitations, e.g., polyUb chains attach to the acceptor protein (Faggiano et al., ). Chemical protein synthesis has been extensively developed to overcome these limitations (Mali et al., ; Gui et al., ; Huppelschoten and van der Heden van Noort, ). Three strategies have been developed for the chemical synthesis of native isopeptide bonds: Auxiliary mediated ligation, first reported by Muir (Chatterjee et al., ); ´-mercaptolysine- (Kumar et al., ) or ³-mercaptolysine- (Yang et al., ; Merkx et al., ) mediated ligation; and isoUb ligation (Tang et al., ).

´-Mercaptolysine-mediated ligation has been extensively used for the synthesis of diUb chains (Kumar et al., ), tetra-ubiquitinated peptides (Bavikar et al., ),

  • 職務経験. Professor. 高知大学. 年4月 – 現在
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    • Bletia: Promisified BluetoothGatt wrapper library(including JDeferred)
    • RxBletia: RxJava binding APIs for Android's BluetoothGatt

    Use Bletia:

    dependencies { // use Bletia compile 'd:bletia' }

    Use RxBletia:

    dependencies { // use RxBletia compile 'd:bletia' compile 'vex:rxjava' }
    // Pass application context to bletia = newBletia(context);
    // BluetoothDevice t(device);
    // BluetoothGattCharacteristic characteristic Notification(characteristic, true) .then(newDoneCallback<BluetoothGattCharacteristic>() { @OverridepublicvoidonDone(BluetoothGattCharacteristicresult) { // Call when the request was successfully. } }) .fail(newFailCallback<BletiaException>() { @OVerridepublicvoidonFail(BletiaExceptionresult) { // Call when the request was failure. } });
    // BluetoothGattCharacteristic characteristic aracteristic(characteristic) .then(newDoneCallback<BluetoothGattCharacteristic>() { @OverridepublicvoidonDone(BluetoothGattCharacteristicresult) { // Call when the request was successfully. } }) .fail(newFailCallback<BletiaException>() { @OVerridepublicvoidonFail(BletiaExceptionresult) { // Call when the request was failure. } });
    // BluetoothGattCharacteristic haracteristic(characteristic) .then(newDoneCallback<BluetoothGattCharacteristic>() { @OverridepublicvoidonDone(BluetoothGattCharacteristic