Design and synthesis of a crosslinker for studying intracellular steroid trafficking pathways.

ABSTRACT: A crosslinker was designed and synthesized as a molecular tool for potential use in probing the intracellular trafficking pathways of steroids. The design was guided by computational modeling based upon a model for the transfer of cholesterol between two proteins, NPC1 and NPC2. These proteins play critical roles in the transport of low-density lipoprotein-derived cholesterol from the lumen of lysosomes to other subcellular compartments. Two modified cholesterol residues were covalently joined by a tether based on molecular modeling of the transient interaction of NPC1 and NPC2 during the transfer of cholesterol from the binding site of one of these proteins to the other. With two cholesterol molecules appropriately connected, we hypothesize that the cholesterol binding sites of both prote

SUBMITTER: Byrd KM 

PROVIDER: S-EPMC4461494 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature