title: Anion transport properties of amine and amide-sidechained peptides are affected by charge and phospholipid composition.
abstract: Four synthetic anion transporters (SATs) having the general formula (n-C(18)H(37))(2)N-COCH(2)OCH(2)CO-(Gly)(3)Pro-Lys(epsilon-N-R)-(Gly)(2)-O-n-C(7)H(15) were prepared and studied. The group R was Cbz, H (TFA salt), t-Boc, and dansyl in peptides 1, 2, 3, and 4 respectively. The glutamine analog (GGGPQAG sequence) was also included. A dansyl-substituted fluorescent SAT was used to probe peptide insertion; the dansyl sidechain resides in an environment near the bilayer's midpolar regime. When the lysine sidechain was free or protected amine, little effect was noted on final Cl(-) transport rate in DOPC : DOPA (7 : 3) liposomes. This stands in contrast to the significant retardation of transport previously observed when a negative glutamate residue was present in the peptide sequence. It was also found that Cl(-) release from liposomes depended on the phospholipid composition of the vesicles. Chloride transport diminished significantly for the free lysine containing SAT, 2, when the lipid was altered from DOPC : DOPA to pure DOPC. Amide-sidechained SATs 1 and 5 showed a relatively small decrease in Cl(-) transport. The effect of lipid composition on Cl(-) transport was explained by differences in electrostatic interaction between amino acid sidechain and lipid headgroup, which was modeled by computation.
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.forename: Ruiqiong
authors.initials: R
authors.lastname: Li
authors.forename: George W
authors.initials: GW
authors.lastname: Gokel
mesh_terms: D000577:Amides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D003198:Computer Simulation; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D008081:Liposomes / Q000138:chemical synthesis; D015394:Molecular Structure; D027361:Organic Anion Transporters / Q000138:chemical synthesis*; D010455:Peptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*
chemical_list: D000577:Amides; D000588:Amines; D005456:Fluorescent Dyes; D008081:Liposomes; D027361:Organic Anion Transporters; D010455:Peptides; D010713:Phosphatidylcholines; D010743:Phospholipids; C017251:1,2-oleoylphosphatidylcholine