Structure/activity study of tris(2-aminoethyl)amine-derived translocases for phosphatidylcholine.

Content Provider	Semantic Scholar
Author	Boon, Josua Lambert, Timothy N. Smith, Bradley D. Beatty, Alicia M. Ugrinova, Vesela Brown, Seth N.
Copyright Year	2002
Abstract	Sulfonamide and amide derivatives of tris(aminoethyl)amine (TREN) are known to facilitate phospholipid translocation across vesicle and erythrocyte membranes; that is, they act as synthetic translocases. In this report, a number of new TREN-based translocases are evaluated for their abilities to bind phosphatidylcholine and translocate a fluorescent phosphatidylcholine probe. Association constants were determined from (1)H NMR titration experiments, and translocation half-lives were determined via 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)/dithionite quenching assays. A rough correlation exists between translocase/phosphatidylcholine association constants and translocation half-lives. The tris-sulfonamide translocases are superior to the tris-amide versions because they associate more strongly with the phospholipid headgroup. The stronger association is due to the increased acidity of the sulfonamide NHs as well as a molecular geometry (as shown by X-ray crystallography) that is able to form tridentate complexes with one of the phosphate oxygens. Two fluorescent translocase analogues were synthesized and used to characterize membrane partitioning properties. The results indicate that the facilitated translocation of phospholipids by TREN-derived translocases is due to the formation of hydrogen-bonded complexes with the phospholipid headgroups. In the case of zwitterionic phosphatidylcholine, it is the neutral form of the translocases that rapidly associates with the phosphate portion of the phosphocholine headgroup. Complexation masks the headgroup polarity and promotes diffusion of the phospholipid-translocase complex across the lipophilic interior of the membrane.
Starting Page	207
Ending Page	221
Page Count	15
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www3.nd.edu/~bsmith3/pdf/JOC2002b.pdf
PubMed reference number	11925224v1
Volume Number	67
Issue Number	7
Journal	The Journal of organic chemistry
Language	English
Access Restriction	Open
Subject Keyword	Antiphospholipid Syndrome Carbamoyl-Phosphate Synthase I Deficiency Disease Computed Tomography Scanning Systems Crystallography Erythrocyte Membrane Erythrocytes Phosphatidylcholines Phospholipids Phosphorylcholine Sulfonamide:PrThr:Pt:Ser/Bld:Ord Sulfonamides Tissue membrane Titration Method Tris(2,3-dibromopropyl) Phosphate Tromethamine Version Vesicle (morphologic abnormality) inorganic phosphate lipophilicity polarity translocase tris(2-aminoethyl)amine
Content Type	Text
Resource Type	Article