Amphiphilic poly(meta-phenylene)s: A novel conjugated polysoap; A possible foldamer?

Novel amphiphilic poly(meta-phenylene)s were prepared by an oxidative coupling approach. These polymers were synthesized to shed light on their solution properties with special emphasis on aggregation and folding behavior. The polymers were characterized by NMR spectroscopy and molecular weights were determined by Gel Permeation Chromatography using Universal calibration. Literature studies revealed that the backbone of these PMPs can be helical moreover, the light emitting properties of this conjugated polymer can be used as a handle to study the possible aggregation or self-assembling behavior. In this report we show the synthesis, characterization and preliminary aggregation properties that points out that one of the synthesized PMP behave as a polysoap.

Gabapentin: A Stereochemically Constrained gamma Amino Acid Residue in Hybrid Peptide Design

Nature has used the all-alpha-polypeptide backbone of proteins to create a remarkable diversity of folded structures. Sequential patterns of 20 distinct amino adds, which differ only in their side chains, determine the shape and form of proteins. Our understanding of these specific secondary structures is over half a century old and is based primarily on the fundamental elements: the Pauling alpha-helix and beta-sheet. Researchers can also generate structural diversity through the synthesis of polypeptide chains containing homologated (omega) amino acid residues, which contain a variable number of backbone atoms. However, incorporating amino adds with more atoms within the backbone introduces additional torsional freedom into the structure, which can complicate the structural analysis. Fortunately, gabapentin (Gpn), a readily available bulk drug, is an achiral beta,beta-disubstituted gamma amino add residue that contains a cyclohexyl ring at the C-beta carbon atom, which dramatically limits the range of torsion angles that can be obtained about the flanking C-C bonds. Limiting conformational flexibility also has the desirable effect of increasing peptide crystallinity, which permits unambiguous structural characterization by X-ray diffraction methods. This Account describes studies carried out in our laboratory that establish Gpn as a valuable residue in the design of specifically folded hybrid peptide structures. The insertion of additional atoms into polypeptide backbones facilitates the formation of intramolecular hydrogen bonds whose directionality is opposite to that observed in canonical alpha-peptide helices. If hybrid structures mimic proteins and biologically active peptides, the proteolytic stability conferred by unusual backbones can be a major advantage in the area of medicinal chemistry. We have demonstrated a variety of internally hydrogen-bonded structures in the solid state for Gpn-containing peptides, including the characterization of the C-7 and C-9 hydrogen bonds, which can lead to ribbons in homo-oligomeric sequences. In hybrid alpha gamma sequences, district C-12 hydrogen-bonded turn structures support formation of peptide helices and hairpins in longer sequences. Some peptides that include the Gpn residue have hydrogen-bond directionality that matches alpha-peptide helices, while others have the opposite directionality. We expect that expansion of the polypeptide backbone will lead to new classes of foldamer structures, which are thus far unknown to the world of alpha-polypeptides. The diversity of internally hydrogen-bonded structures observed in hybrid sequences containing Gpn shows promise for the rational design of novel peptide structures incorporating hybrid backbones.