Effect of the spacer on the structure and self-assembly of FF peptide mimetics.

We have designed and synthesized a series of FF peptide mimetics with conformationally rigid and flexible spacers to study the effect of spacers on their structure and self-assembly. The results help in understanding biomolecular aggregation and provide a strategy to obtain fractal pattern materials. From X-ray single crystal analysis, the m-diaminobenzene appended FF peptide mimetic adopts a duplex structure stabilized by multiple intermolecular hydrogen bonds. There is also a water molecule bridging between two strands of the duplex. Moreover, the duplex is stabilized by three face-to-face, face-to-edge and edge-to-edge π-π interactions. The duplex formation is also supported by mass spectrometry. In higher order packing, the dimeric subunits further self-assembled to form a complex sheet-like structure stabilized by multiple intermolecular hydrogen bonding and π-π stacking interactions. Moreover, the 1,4-butadiene and m-xylylenediamine appended FF peptide mimetics form stimuli-responsive organogels in a wide range of solvents including methanol. The rheology data of FF peptide mimetic gels as a function of angular frequency and oscillatory strain also supported the formation of strong physically crosslinked gels. The FE-SEM images of the xerogels obtained from different organic solvents show that the network morphology of FF peptide mimetics varies depending on the nature of the solvents.

Asymmetric rotations and dimerization driven by normal to modulated phase transition in 4-biphenylcarboxy coupled L-phenylalaninate.

Amongst the derivatives of 4-biphenylcarboxylic acid and amino acid esters, the crystal structure of 4-biphenylcarboxy-(L)-phenylalaninate is unusual owing to its monoclinic symmetry within a pseudo-orthorhombic crystal system. The distortion is described by a disparate rotational property around the chiral centers (ϕchiral ≃ -129° and 58°) of the two molecules in the asymmetric unit. Each of these molecules comprises planar biphenyl moieties (ϕbiphenyl = 0°). Using temperature-dependent single-crystal X-ray diffraction experiments we show that the compound undergoes a phase transition below T ∼ 124 K that is characterized by a commensurate modulation wavevector, q = δ(101), δ = ½. The (3+1)-dimensional modulated structure at T = 100 K suggests that the phase transition drives the biphenyl moieties towards noncoplanar conformations with significant variation of internal torsion angle (ϕmaxbiphenyl ≤ 20°). These intramolecular rotations lead to dimerization of the molecular stacks that are described predominantly by distortions in intermolecular tilts (θmax ≤ 20°) and small variations in intermolecular distances (Δdmax ≃ 0.05 Å) between biphenyl molecules. Atypical of modulated structures and superstructures of biphenyl and other polyphenyls, the rotations of individual molecules are asymmetric (Δϕbiphenyl ≈ 5°) while ϕbiphenyl of one independent molecule is two to four times larger than the other. Crystal-chemical analysis and phase relations in superspace suggest multiple competing factors involving intramolecular steric factors, intermolecular H-C...C-H contacts and weak C-H...O hydrogen bonds that govern the distinctively unequal torsional properties of the molecules.

Enhancing the optical response and biosensing capabilities of bioinspired peptide micro-waveguides exploiting chromatic aberration.

Bioinspired peptide waveguides of mesoscopic length scales have established a new paradigm in photonics with possible applications in precision bioimaging, sensing, and diagnostics. Here, we improve the efficiency of coupling various constituent colors of a white light source into single self-assembled microtube-shaped passive peptide waveguides by employing chromatic aberration. Thus, we use a chromatically aberrated microscope objective lens to couple light into peptide waveguides. Using both numerical simulation and experiments, we show that the waveguide response displays higher quality factor, wavelength selectivity, and axial coupling range compared to a chromatically corrected standard plan-fluoritic objective lens. We also demonstrate absorption and refractive index-based sensing by studying the changes in the optical responses of the peptide tubes in the presence of a wide concentration range of the absorptive Congo red, and the nonabsorptive Coumarin dyes. The former understandably display a much higher response than the latter due to the low finesse of the waveguides. We obtain a detection limit of around 10 nM for Congo red, and 10 mM for Coumarin. Our study opens up possibilities for deploying such peptide microtubes for various biosensing applications utilizing spectral and waveguide characteristics.

Synthesis and structural investigation of 2-aminomethyl-3-(4-methoxy-phenyl)-propionic acid containing a peptide analogue of the amyloidogenic AS(6-7) sequence: inhibition of fibril formation.

The incorporation of a single ß-amino acid moiety in a highly amyloidogenic peptide sequence resulted in the complete inhibition of amyloid fibril formation. The Boc-l-Phe-l-Leu-OMe sequence 1, which has sequence identity with the N-terminal AS(6-7) of the non-immunoglobulin amyloid fibril protein AS, which is responsible for rheumatoid arthritis, self-associates to produce fibrils. The d-Phe analogue peptide 2 shows an elongated ribbon-like morphology. However, the 2-aminomethyl-3-(4-methoxy-phenyl)-propionic acid containing analogue peptide 3 exhibits a polydisperse microsphere morphology. Moreover, fibrils from peptides 1 and 2 exhibit typical green-gold birefringence upon Congo red (CR) staining and show an amyloid-like morphological resemblance. However, the 2-aminomethyl-3-(4-methoxy-phenyl)-propionic acid modified peptide 3 does not respond to the Congo red assay. From X-ray crystallography, peptide 1 with the l-Phe residue adopts an extended structure, whereas the d-Phe analogue 2 adopts a kink-like structure. Both peptides 1 and 2 show twisted anti-parallel sheet-like structures at higher order assembly. However, peptide 3 adopts a nine-membered hydrogen bonded δ-turn-like structure in the solid state and self-associates to form a loop-like supramolecular structure through multiple intermolecular hydrogen bonds. The structural analysis presented herein may foster new studies for de novo design and therapeutics.

Mopping up the Oil, Metal, and Fluoride Ions from Water.

The recycle, cleaning, and reuse of water are highly important for environmental remediation. This issue is addressed by creating a fluorescent zwitterionic spirocyclic Meisenheimer complex with high chelating propensity for toxic metals using low-cost starting materials and a one-pot synthesis technique. The resulting material is able to detect fluoride up to 12.8 ppb level and remove 82% aqueous fluoride from 1000 mL of 100 ppm fluoride solution in a single contact. The material demonstrates rapid kinetics and is capable of dropping the toxic metal ion (Pb/Hg/Cd) concentration below 0.2 ppb within 10 min. A resin-free, precipitation-free, and reusable technique has been developed for the removal of toxic metal ions and fluoride from extremely polluted water. Moreover, utilizing its extreme hydrophobicity, polystyrene sponges have been coated with the Meisenheimer complex to mop up oil spill and organic solvents from a biphasic mixture.

Assembly, growth and nonlinear thermo-optical properties of nitropeptides.

The molecular self-assembly, growth and nonlinear thermo-optical properties of three synthetic aromatic­aliphatic hybrid nitropeptides have been investigated. The X-ray crystallography of nitropeptide 2 containing a glutamic acid moiety shows that the peptide adopts a dimeric structure using intermolecular hydrogen bonding as well as face to face π­π stacking interactions. Moreover, nitropeptide 2 exhibits nonlocal nonlinear optical properties. When a Gaussian laser beam passes through nitropeptide 2, the peptide shows several concentric rings due to spatial self-phase modulation (SSPM). However, the homologous peptide 1 containing an aspartic acid moiety and peptide 3 containing an achiral α-aminoisobutyric acid (Aib) moiety adopt sheet-like structures and have no self-phase modulation effect. The report describes the thermo-optical properties consistent with assumption and calculation and is promising for their applications in nonlinear optical modulation devices.

Supramolecular double helix from capped γ-peptide.

The single crystal X-ray diffraction study of capped γ-peptide reveal that the peptide adopts helical conformation which self-assemble to form a supramolecular parallel double helical structure using intermolecular hydrogen bonding as well as π-π stacking interactions in the solid state.

Fabrication of hollow self-assembled peptide microvesicles and transition from sphere-to-rod structure.

This paper presents the construction of hollow peptide microspheres and the mechanism of transition of microspheres to rod-like vesicles at low concentration. The tripeptides Boc-Phe-Maba-Phe-OMe 1 and Boc-Phe-Maba-Tyr-OMe 2, each of them containing a rigid m-aminobenzoic acid (Maba) template at the central position, forms microspheres at a concentration of 1.6 mM in methanol. At low concentration, these vesicular structures are fused through neck formation, and this leads to sphere-to-rod transition of vesicles. Sizes of these microspheres increase with increasing concentration. We have successfully characterized this transition by fluorescence spectroscopy, DLS, and electron microscopic study. The scanning electron microscopy clearly shows that these spheres are hollow. One important property of these microvesicular structures is the encapsulation of a potent anticonvulsant and mood stabilizing drug carbamazepine, which holds future promise to use these microvesicles as delivery vehicles.

The role of the disulfide bond in amyloid-like fibrillogenesis in a model peptide system.

Three terminally protected short peptides Bis[Boc-D-Leu1-Cys2-OMe] 1, Bis[Boc-Leu1-Cys2-OMe] and Bis[Boc-Val1-Cys2-OMe] 3 exhibit amyloid-like fibrillar morphology. Single crystal X-ray diffraction analysis of peptide 1 clearly demonstrates that it adopts an overall extended backbone molecular conformation that self-assembles to form an intermolecular hydrogen-bonded antiparallel supramolecular beta-sheet structure in crystals. Scanning electron microscopic (SEM) images, transmission electron microscopic (TEM) images and Congo red binding studies vividly demonstrate the amyloid-like fibril formation of peptides 1, 2 and 3. However, after reduction of the disulfide bridge of peptides 1, 2 and 3, three newly generated peptides Boc-D-Leu1-Cys2-OMe 4, Boc-Leu1-Cys2-OMe 5 and Boc-Val1-Cys2-OMe 6 are formed and all of them failed to form any kind of fibril under the same conditions, indicating the important role of the disulfide bond in amyloid-like fibrillogenesis in a peptide model system.

Peptide-assisted synthesis of gold nanoparticles and their self-assembly.

A novel gold nanoparticle-tripeptide (GNP-tripeptide) conjugate was prepared by peptide in-situ redox technique at ambient temperatureusing a newly designed tripeptide. This new tripeptide was nso designed that it has a C-terminus tyrosine residue, which reduced Au+3 to Au, and the terminally located free amino group was bound to the gold nanoparticle (GNP) surface resulting in highly stable Au colloids. The average diameter of the tripeptide-stabilized GNP is 8.7 +/- 2.3 nm. Tripeptide bound gold nanoparticles formed three-dimensional assemblies in the presence of an excess of similar or disimilar tripeptides. The aggregation of GNPs results in a red shift in the surface plasmon resonance from lambda max = 527 to 556 nm. The effect of the solvent, concentration, and nature of the tripeptides on the assembly process were investigated by TEM and UV-visible spectroscopy.

X-ray crystallographic signature of supramolecular triple helix formation from a water soluble synthetic tetrapeptide.

Single crystal X-ray diffraction studies on the water soluble, synthetic tetrapeptide Tyr(1)-Aib(2)-Tyr(3)-Val(4) with a non-coded amino acid residue (Aib: [small alpha]-amino isobutyric acid) reveal that the peptide adopts an "S"-shaped molecular structure which self-assembles to form a supramolecular triple helix using various non-covalent interactions including water mediated hydrogen bonds in the solid state.