31918-50-0Relevant academic research and scientific papers
Multifunctional dinucleotide analogs for the generation of complex RNA conjugates
Hausch, Felix,J?schke, Andres
, p. 1261 - 1268 (2001)
Oligonucleotide conjugates are needed for in vitro selection schemes aiming at reactions between small, organic reactants. A general strategy is provided for the generation of the required RNA reactant conjugates based on multifunctional dinucleotide anal
Identification of a peptoid inhibitor of the proteasome 19S regulatory particle
Lim, Hyun-Suk,Archer, Chase T.,Kodadek, Thomas
, p. 7750 - 7751 (2007)
The first chemical inhibitor of the 19S regulatory particle (RP) of the proteasome is described. The molecule was identified by screening a library of nucleoside-capped peptoids for binding to the yeast 26S proteasome in a crude extract. The hit was resynthesized and shown to block 19S RP-mediated protein unfolding in vitro and proteasome-mediated turnover of p27 in HeLa cells. Copyright
Converting a weaker ATP-binding site inhibitor into a potent hetero-bivalent ligand by tethering to a unique peptide sequence derived from the same kinase
Kedika, Samanth Reddy,Udugamasooriya, D. Gomika
supporting information, p. 6443 - 6449 (2018/10/02)
Attaching an additional binding site directed moiety or a ligand to an ATP-binding site inhibitor has been used as a strategy to increase kinase binding affinity and specificity. The moieties typically used here as the second binding partner are varied from simple organic groups to ligands such as peptides derived from substrate binding site sequences. So far these hetero-bivalent ligands were developed targeting additional binding sites closer to the ATP-binding pocket. Here we report a unique expansion of this hetero-bivalent idea by: (I) targeting a new binding site much farther away from ATP-binding site, (II) using a peptide uniquely derived from a portion of the same kinase sequence that has been reported to turn and bind to the above distance binding pocket (used as the second binding ligand), and (III) optimizing a much longer and flexible linker (to connect ATP-binding site inhibitor and above mentioned second peptide sequence) with multistep, yet complete on-bead synthesis approach. We converted a very weak EphA3-kinase ATP-binding site inhibitor-PP2 into a potent hetero-bivalent ligand by tethering to a unique 5-mer peptide sequence that derived from the linker region of EphA3 that connects kinase and sterile alpha motif (SAM) domains. Our design highlight the use of distance binding pockets to ATP-binding site as the second targeted site, while introducing the idea of extracting natural peptide sequences that already exist within the same kinase sequence, by a careful screening of available crystal structures.
