title: Solid-phase synthesis of Biotin-S-Farnesyl-L-Cysteine, a surrogate substrate for isoprenylcysteine Carboxylmethyltransferase (ICMT).
abstract: Inhibition of isoprenylcysteine Carboxylmethyltransferase (ICMT) is of particular interest as a potential target for the development of cancer chemotherapeutic agents. Screening for inhibitors of ICMT utilises a scintillation proximity assay (SPA) in which Biotin-S-Farnesyl-L-Cysteine (BFC) acts as a surrogate substrate. A solid-phase synthesis protocol for the preparation of BFC using 2-chlorotrityl chloride resin as a solid support has been developed to provide sufficient supply of BFC for high throughput screening (HTS) and subsequent chemistry campaigns to target inhibitors of ICMT. The BFC prepared by this method can be produced quickly on large scale and is stable when stored at -20 °C as a solid, in solution, or on the resin.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland 4111, Australia. Electronic address: g.stevenson@griffith.edu.au.
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Stevenson
authors.forename: Sarah
authors.initials: S
authors.lastname: Yong
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Fechner
authors.forename: Juliette
authors.initials: J
authors.lastname: Neve
authors.forename: Aaron
authors.initials: A
authors.lastname: Lock
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Avery
mesh_terms: D001710:Biotin / Q000737:chemistry*; D003545:Cysteine / Q000138:chemical synthesis / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D007700:Kinetics; D011496:Protein Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D060327:Solid-Phase Synthesis Techniques; D013379:Substrate Specificity; D014320:Triphenylmethyl Compounds / Q000737:chemistry
chemical_list: D014320:Triphenylmethyl Compounds; C071065:2-chlorotrityl chloride; D001710:Biotin; D011496:Protein Methyltransferases; C056501:protein-S-isoprenylcysteine O-methyltransferase; D003545:Cysteine
keywords: Biotin-S-Farnesyl-l-Cysteine (BFC); DMF; HBTU; HOBt; Isoprenylcysteine Carboxylmethyltransferase (ICMT); N,N-dimethylformamide; O-benzotriazole-N,N,N′, N′-tetramethyluronium hexafluoro-phosphate; Prenylation; S-adenosyl-l-homocysteine; S-adenosyl-l-methionine; S:N; SAH; SAM; hydroxy-benzotriazole; signal to noise