Biomedical subjects

Morris M Slutsky

Publications and source records attributed to Morris M Slutsky.

4 recordsLinked to original sources

PubMed2007

Spin system assignment of homo-o-phenylene ethynylene oligomers.

We previously reported the synthesis and solution characterization of short o-phenylene ethynylene (oPE) foldamers. Proton correlation techniques are not adequate for NMR assignment in these compounds as the ethynylene linkers interrupt proton connectivity. In order to facilitate structural characterization and more fully harness the power of NMR, it is necessary to know the sequence of spin systems along the molecular backbone. For example, spin system assignment is required to unambiguously assign NOE correlations for structural determination of folded forms in solution. Therefore, we developed a method to assign the aromatic spin systems in these compounds using HMBC experiments. This has been performed for tetrameric (Es4), pentameric (Es5), and hexameric (Es6) oligomers and is expected to prove useful for this class of foldamers in general. The proton assignments obtained by this technique have been useful toward confirming the previous hypotheses of helical folding in oPE systems.

Alkynes↗

PubMed2005

Solution 1H NMR confirmation of folding in short o-phenylene ethynylene oligomers.

Oligomers based on an o-phenylene ethynylene (oPE) backbone with polar substituents have been synthesized using Sonogashira methods. Folding of these extremely short oligomers was confirmed via 1D and 2D (NOESY) NMR methods. Utilizing electron-rich and electron-poor phenylene building blocks, variations of these oPE oligomers have been synthesized to determine the folded stability of pi-rich vs pi-poor vs pi-rich-pi-poor systems. Slight variations in temperature offer a route, aside from solvent denaturation, to probe the stability of the folded structure. This is the first report of an NMR solution characterization of folding for a PE backbone without hydrogen bonds.

Alkynes↗

PubMed2004

Fluorous effect in proteins: de novo design and characterization of a four-alpha-helix bundle protein containing hexafluoroleucine.

Several studies have demonstrated that proteins incorporating fluorinated analogues of hydrophobic amino acids such as leucine and valine into their hydrophobic cores exhibit increased stability toward thermal denaturation and unfolding by guanidinium chloride. However, estimates for the increase in the thermodynamic stability of a protein (DeltaDeltaG(unfold)) afforded by the substitution of a hydrophobic amino acid with its fluorinated analogue vary quite significantly. To address this, we have designed a peptide that adopts an antiparallel four-helix bundle structure in which the hydrophobic core is packed with leucine, and investigated the effects of substituting the central two layers of the core with L-5,5,5,5',5',5'-hexafluoroleucine (hFLeu). We find that DeltaDeltaG(unfold) is increased by 0.3 kcal/mol per hFLeu residue. This is in good agreement with the predicted increase in DeltaDeltaG(unfold) of 0.4 kcal/mol per residue arising from the increased hydrophobicity of the hFLeu side chain, which we determined experimentally from partitioning measurements on hFLeu and leucine. The increased stability of this fluorinated protein may therefore be ascribed to simple hydrophobic effects, rather than specific "fluorous" interactions between the hFLeu residues.

Circular Dichroism↗

PubMed2004

Cation-pi interactions studied in a model coiled-coil peptide.

Cation-pi interactions between aromatic amino acids and the positively charged residues lysine and arginine have been proposed to play an important role in stabilizing protein structure. We have used a peptide that adopts a coiled coil structure as a model system to evaluate the energetic contribution of cation-pi interactions to protein folding. Peptides were designed in which phenylalanine, tyrosine, and tryptophan were placed at a solvent-exposed position of the helix, one turn removed from an arginine residue that could provide a favorable cation-pi interaction. Only the arginine-phenylalanine pairing provided significant stabilization of the peptide structure and it appears that hydrophobic packing, rather than the cation-pi effect, is more likely to be responsible for the stability of this peptide. We conclude that any stabilizing effect of cation-pi interactions in these peptides is much smaller than that predicted from computational studies.

Amino Acids↗