112918-82-8Relevant articles and documents
Chemical evidence for transbilayer movement of molecular umbrellas
Shawaphun, Sarinya,Janout, Vaclav,Regen, Steven L.
, p. 5860 - 5864 (1999)
Chemical evidence has been obtained for transbilayer movement of a di- walled and a tetra-walled molecular umbrella in large unilamellar vesicles (200 nm) derived from 1-palmitoyl-2-oleyol-sn-glycero-3-phoshatidylglycerol (POPG). A di-walled molecular umbrella (1), bearing 2-mercaptopyridine (2- MP) as a 'reactive tag', was synthesized by reaction of N1,N3- spermidinebis[cholic acid amide] (3) with [N-1,2,3-benzotriazin-4(3H)one- yl]-3-(2-pyridyldithio)propionate [BPDP]. An analogous tetra-walled umbrella (2) was also prepared by condensing Fmoc-protected iminodiacetic acid with two molecules of 3, deprotecting the secondary amino group, and coupling the resulting intermediate (4) with BPDP. Reaction of vesicle-bound 1 with external glutathione (GSH) resulted in a rapid and quantitative release of 2- MP. A similar thiolate - disulfide interchange reaction that was carried out between membrane-bound 1 and GSH, which was captured within the aqueous interior of the vesicles, also resulted in rapid and complete release of 2- MP. These results, together with the fact that GSH does not permeate across the POPG vesicle membranes, provides compelling evidence for rapid transbilayer movement. Reaction of membrane-bound 2 with external GSH also resulted in the rapid and quantitative release of 2-MP. The significance of these findings, with regard to the current view of molecular size restrictions on membrane permeability, is briefly discussed.
Adenosine receptor prodrugs
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, (2008/06/13)
A functionalized congener approach to drugs acting at A 1 and A 2 adenosine receptor types is applicable to prodrug design. The prodrugs affect a more efficient delivery of the drug at the particular site of the body affected and take advantage of selective biochemical cleavages and alteration in distribution characteristics. In particular, kidney functions and lipid functions are stressed in the invention.
