Solid‐Phase Syntheses of Unnatural Biopolymers Containing Repeating Urea Units

Abstract

COMMUNICATIONSto understand the mechanism by which metal binding induces dispersion of the lipid aggregates and investigations of the generality of this type of sensor are underway. Experimental ProcedureStock lipid solutions were made by dissolving lipids and cholesterol (Sigma) in CHCI, (HPLC grade). Lipid I or 2 and a matrix lipid (DSPC, SOPC, or I:1 DSPC:cholesterol) were combined (5 mol% lipid I or 2 , 9 5 mol% matrix lipid) to give 10 pmol total lipid in l2mL volumetric centrifuge tubes. The lipid mixture was concentrated under aspirator vacuum, and 3 mL of MOPS buffer ( 2 0 m~ MOPS, 0.1 M NaCI. pH 7.5) was added to the tubes. The tubes were heated above 55°C and sonicated with a probe tip (Heat Systems model 375) for 15 min at 25-35% power under argon atmosphere in an ice bath. The vesicles were centrifuged at 11 000 rpm for 20 min to remove titanium particles. The phosphate concentration was determined for selected samples [15]. Vesicle sizes were measured by quasi-elastic light scattering by using a Microtrac Ultrafine Particle Analyzer (Leeds & Northrop) at 25 C in phosphate buffer. The mean diameter was 49 nm (59 nm distribution width) for unmetdlated vesicles. Vesicles were diluted 167-fold in MOPS buffer for metalbinding studies. Steady-state fluorescence measurements were performed at 25 "C on a temperature-controlled Shimadzu RF-450 spectrofluorimeter, excitation at 346 nin. 5 nm excitation and emission slit width.

Isosteric Substitutions of Urea to Thiourea and Selenourea in Aliphatic Oligourea Foldamers: Site‐Specific Perturbation of the Helix Geometry

“…[13,14] In this work, we propose to use the oxo to thioxo (or selenoxo) substitution to interrogate the structure and function of foldamers [15] made of urea linkages instead of amide bonds. [16,17] Oligoureas consisting of chiral ethylene diamine units connected by a carbonyl group are known to adopt a regular helical structure (2.5-helix) maintained by a network of three centered hydrogen bonds closing 12-and 14-membered pseudocycles.…”

Biological Applications of Foldamers

“…The presence of an additional H-bond interaction makes the backbone more rigid compared to aryl amides. Several procedures have been described for the synthesis of urea oligomers, including on solid support via activated carbamate intermediates [131][132][133] and single-pot reactions using carbonyl diimadazole couplings [134]. 8.1.6 meta-Phenylene Ethynylenes (mPE) meta-Phenylene ethynylenes (mPE) are hydrocarbon scaffolds composed of phenyl rings connected by ethynylene linkages at the meta position ( Fig.…”

Solid‐Phase Synthesis of Hybrid Urea Oligomers Containing Conservative Thiourea Mutations

“…The synthesis of homooligoureas has been studied extensively over the last 15 years, and various methods for their solid-supported synthesis have been reported by our group [21][22][23] and others. [24][25][26][27][28] In our laboratory, the SPS of oligoureas with chain lengths ranging from 6-12 residues is now routinely achieved using succinimidyl (2-substituted 2-azidoethyl)carbamates of type A (Figure 2). [23] The advantage of these activated monomers compared to corresponding N-Fmoc-and N-Boc-protected (Fmoc = fluorenylmethoxycarbonyl; Boc = tert-butoxycarbonyl) building blocks (B; Figure 2) is that they can be used with standard TFA-labile resins (TFA = trifluoroacetic acid), and also that they can be used in conjunction with microwave irradiation to accelerate the oligourea-chain extension.…”