146462-58-0Relevant articles and documents
Ligand-Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand
Kawamura, Shuhei,Ito, Yoshihiko,Hirokawa, Takatsugu,Hikiyama, Eriko,Yamada, Shizuo,Shuto, Satoshi
, p. 4020 - 4029 (2018/05/07)
We hypothesized that if drug localization can be restricted to a particular subcellular domain where their target proteins reside, the drugs could bind to their target proteins without being metabolized and/or excreted, which would significantly extend the half-life of the corresponding drug-target complex. Thus, we designed ligand-phospholipid conjugates in which the ligand is conjugated with a phospholipid through a polyethylene glycol linker to restrict the subcellular localization of the ligand in the vicinity of the lipid bilayer. Here, we present the design, synthesis, pharmacological activity, and binding mode analysis of ligand-phospholipid conjugates with muscarinic acetylcholine receptors as the target proteins. These results demonstrate that ligand-phospholipid conjugation can be a versatile strategy for developing long-acting ligands that bind to membrane proteins in drug discovery.
Synthesis of New Glycerolipids Linked to Hydroxamate Derivatives Designed for Two-Dimensional Crystallization of Aminopeptidase M
Altenburger, Jean-Michel,Lebeau, Luc,Mioskowski, Charles,Schirlin, Daniel
, p. 2538 - 2544 (2007/10/02)
The synthesis of glycerolipids linked to hydroxamate derivatives designed for two-dimensional crystallization of aminopeptidase M is reported.The lipid moieties are readily obtained using a convergent pathway.Their structure allows the introduction of a w
