Understanding the conformational analysis of gababutin based hybrid peptides.

Constrained γ-amino acid gababutin (Gbn) based peptides that form different conformations have been synthesized. Striving to rationalize the impact of side chain orientations framing tetrapeptide-based supramolecular organic frameworks and morphological entities, Gbn incorporated hybrid peptides Boc-Gbn-Aib-Aaa-Aib-OMe (where Aaa = Phe(F) for peptide 1, Leu(L) for peptide 2 and Tyr(Y) for peptide 3) were synthesized by changing the amino acid at the third position. The solution state dual folded conformation (C12/C10 H-bonded) is probed by 2D NMR spectroscopy in support of a DMSO-d6 titration and VT NMR experiments. Peptides 1-3 adopt a C12/C10 type H-bonded dual folded conformation in the crystal state. In addition, distinct supramolecular frameworks result from the modification and orientation of the third residue side chain of peptides 1-3. A solvent induced morphological diversity of peptides 1-3 is attained by modifying the side chain backbone of the tetrapeptides, which are investigated by various microscopic (SEM and AFM) studies. Gbn-based peptides 1-3 show significant morphological and supramolecular packing properties, which are fairly different from those of their gabapentin (Gpn) based analogue peptides.

Structural and morphological diversity of self-assembled synthetic γ-amino acid containing peptides.

Regulating the nanostructural morphology of synthetic hybrid peptides through external stimuli is still a great challenge. Here, we report the synthesis of constrained amino acid building block gabapentin (Gpn) based hybrid peptides and their structural and morphological diversity in different conditions. The synthesized three hybrid peptides Boc-Gpn-Aib-Phe-Aib-OMe (P), Boc-Gpn-Aib-Leu-Aib-OMe (P) and Boc-Gpn-Aib-Tyr-Aib-OMe (P) are folded into C12/C10 hydrogen-bonded double turn conformations. The double turn feature is probed and confirmed by conformational analysis of hybrid peptides using 2D-NMR studies and X-ray crystallography. DMSO-d6 solvent titration investigations also support the double turn conformation adopted by our reported peptides in CDCl3 solution. Solvent assisted self-assembled morphological features of peptides P-P and the salt-prompted mineralization studies of peptide P under ambient conditions are studied. All three reported peptides P-P form diverse supramolecular scaffolds in solid states through non-covalent interactions to attain higher order architectures.

Lipase-catalyzed dissipative self-assembly of a thixotropic Peptide bolaamphiphile hydrogel for human umbilical cord stem-cell proliferation.

We report lipase-catalyzed inclusion of p-hydroxy benzylalcohol to peptide bolaamphiphiles. The lipase-catalyzed reactions of peptide bolaamphiphiles with p-hydroxy benzylalcohol generate dynamic combinatorial libraries (DCL) in aqueous medium that mimic the natural dissipative system. The peptide bolaamphiphile 1 (HO-WY-Suc-YW-OH) reacts with p-hydroxy benzylalcohol in the presence of lipase forming an activated diester building block. The activated diester building block self-assembles to produce nanofibrillar thixotropic hydrogel. The subsequent hydrolysis results in the dissipation of energy to form nonassembling bolaamphiphile 1 with collapsed nanofibers. The thixotropic DCL hydrogel matrix is used for 3D cell culture experiments for different periods of time, significantly supporting the cell survival and proliferation of human umbilical cord mesenchymal stem cells.

Redox-Active Peptide-Functionalized Quinquethiophene-Based Electrochromic π-Gel.

An electrochromic system based on a self-assembled dipeptide-appended redox-active quinquethiophene π-gel is reported. The designed peptide-quinquethiophene consists of a symmetric bolaamphiphile that has two segments: a redox-active π-conjugated quinquethiophene core for electrochromism, and peptide motif for the involvement of molecular self-assembly. Investigations reveal that self-assembly and electrochromic properties of the π-gel are strongly dependent on the relative orientation of peptidic and quinquethiophene scaffolds in the self-assembly system. The colors of the π-gel film are very stable with fast and controlled switching speed at room temperature.

Controlling Peptide Self-Assembly through a Native Chemical Ligation/Desulfurization Strategy.

Self-assembled peptides were synthesized by using a native chemical ligation (NCL)/desulfurization strategy that maintained the chemical diversity of the self-assembled peptides. Herein, we employed oxo-ester-mediated NCL reactions to incorporate cysteine, a cysteine-based dipeptide, and a sterically hindered unnatural amino acid (penicillamine) into peptides. Self-assembly of the peptides resulted in the formation of self-supporting gels. Microscopy analysis indicated the formation of helical nanofibers, which were responsible for the formation of gel matrices. The self-assembly of the ligated peptides was governed by covalent and non-covalent interactions, as confirmed by FTIR, CD, fluorescence spectroscopy, and MS (ESI) analyses. Peptide disassembly was induced by desulfurization reactions with tris(2-carboxyethyl)phosphine (TCEP) and glutathione at 80 °C. Desulfurization reactions of the ligated peptides converted the Cys and penicillamine functionalities into Ala and Val moieties, respectively. The self-supporting gels showed significant shear-thinning and thixotropic properties.

Peptide self-assembly driven by oxo-ester mediated native chemical ligation.

We use the oxo-ester mediated native chemical ligation (NCL) reaction to generate a peptide self-assembly process to make supramolecular nanofibers and self-supporting gels.