Controlling the G-Quadruplex Topology: Toward the Formation of a Lipid Thrombin Binding Aptamer Prodrug.

Important efforts have been devoted toward the development of modified oligonucleotides capable of controlling the secondary structures of the G-quadruplex (G4). Herein, we introduce a photocleavable, lipidated construct of the well-known Thrombin Binding Aptamer (TBA) whose conformation can be dual-controlled by light and/or the ionic strength of the aqueous solution. This novel lipid-modified TBA oligonucleotide spontaneously self-assembles and switches from the conventional antiparallel aptameric fold at low ionic strength to the parallel, inactive conformation of the TBA oligonucleotide strands under physiologically relevant conditions.

Conformation and Morphology of 4-(NH/OH)-Substituted l/d-Prolyl Polypeptides: Effect of Homo- and Heterochiral Backbones on Formation of β-Structures and Nanofibers.

The relative stereochemistry of C2 and C4 in 4-substituted prolyl polypeptides plays an important role in defining the derived conformation in solution. -(2,4)-Amino/hydroxy-l-prolyl polypeptide (l- /l- ) shows a PPII conformation in phosphate buffer and a β-structure in a relatively hydrophobic solvent, trifluoroethanol (TFE). It is now demonstrated that the homochiral enantiomeric cis-substituted d-prolyl polypeptide (d- /d- ) exhibits mirror image β-structures in TFE.

A disulfide based low molecular weight gel for the selective sustained release of biomolecules.

Constructing biocompatible soft materials via supramolecular approaches remains an important challenge for in vivo applications. Substantial efforts have been made to develop biocompatible non-polymeric materials allowing sustained release of biomolecules and/or drugs in vivo. Herein, we introduce disulfide based low molecular weight gels (LMWGs) allowing the in vitro selective sustained release of proteins containing thiol residues.

Stereodependent and solvent-specific formation of unusual β-structure through side chain-backbone H-bonding in C4(S)-(NH /OH/NHCHO)-L-prolyl polypeptides.

It is shown that C4(S)-NH /OH/NHCHO-prolyl polypeptides exhibit PPII conformation in aqueous medium, but in a relatively hydrophobic solvent trifluoroethanol (TFE) transform into an unusual β-structure. The stereospecific directing effect of H-bonding in defining the specific structure is demonstrated by the absence of β-structure in the corresponding C4(S)-guanidinyl/(NH/O)-acetyl derivatives and retention of β-structure in C4(S)-(NHCHO)-prolyl polypeptides in TFE. The distinct conformations are identified by the characteristic CD patterns and supported by Raman spectroscopic data.

A nanofiber assembly directed by the non-classical antiparallel β-structure from 4S-(OH) proline polypeptide.

The antiparallel arrangement of two strands of the non-classical β-structure, formed exclusively via cis-4S-(OH) prolyl polypeptide as established by FRET, propagates into self-assembled nanofibers upon conjugation with C12/C14/C16 hydrocarbon chains.

Orchestration of Structural, Stereoelectronic, and Hydrogen-Bonding Effects in Stabilizing Triplexes from Engineered Chimeric Collagen Peptides (Pro(X)-Pro(Y)-Gly)6 Incorporating 4(R/S)-Aminoproline.

Collagens are an important family of structural proteins found in the extracellular matrix with triple helix as the characteristic structural motif. The collagen triplex is made of three left-handed polyproline II (PPII) helices with each PPII strand consisting of repetitive units of the tripeptide motif X-Y-Gly, where the amino acids X and Y are most commonly proline (Pro) and 4R-hydroxyproline (Hyp), respectively. A C4-endo pucker at X-site and C4-exo pucker at Y-site have been proposed to be the key for formation of triplex, and the nature of pucker is dependent on both the electronegativity and stereochemistry of the substituent.