Can a consecutive double turn conformation be considered as a peptide based molecular scaffold for supramolecular helix in the solid state?

Helices and sheets are ubiquitous in nature. However, there are also some examples of self-assembling molecules forming supramolecular helices and sheets in unnatural systems. Unlike supramolecular sheets there are a very few examples of peptide sub-units that can be used to construct supramolecular helical architectures using the backbone hydrogen bonding functionalities of peptides. In this report we describe the design and synthesis of two single turn/bend forming peptides (Boc-Phe-Aib-Ile-OMe 1 and Boc-Ala-Leu-Aib-OMe 2) (Aib: alpha-aminoisobutyric acid) and a series of double-turn forming peptides (Boc-Phe-Aib-IIe-Aib-OMe 3, Boc-Leu-Aib-Gly-Aib-OMe 4 and Boc-gamma-Abu-Aib-Leu-Aib-OMe 5) (gamma-Abu: gamma-aminobutyric acid). It has been found that, in crystals, on self-assembly, single turn/bend forming peptides form either a supramolecular sheet (peptide 1) or a supramolecular helix (peptide 2). unlike self-associating double turn forming peptides, which have only the option of forming supramolecular helical assemblages. (c) 2005 Elsevier Ltd. All rights reserved.

Solid state annular tautomerism in a molecule containing two imidazole moieties

The X-ray crystal structure of the 1:2 condensate (1) of hydrazine hydrate and 4-methyl-imidazole-5-carboxaldehyde has been determined. The molecule is centrosymmetric crystallising in the space group Fddd with cell dimensions: a = 10.557(14), b = 17.062(22), c = 24.759(27) angstrom. Fourier map shows that the NH hydrogen atom of each imidazole moiety has equal possibility of occupying any of its two ring N atoms. This poses the possibility of finding three tautomers in 1 in the solid state. Consideration of the H-bonding pattern observed in 1 and related B3LYP/6-311+G(2d, p) calculations show that only two tautomers are present in the solid state. The situation is compared with that in the structure of 4(5)-nitro-5(4)-methoxy-imidazole reported previously by Kubicki.

beta-Sheet mediated self-assembly of dipeptides of omega-amino acids and remarkable fibrillation in the solid state

Single crystal X-ray diffraction studies show that the extended structure of dipeptide I Boc-beta-Ala-m-ABA-OMe (m-ABA: meta-aminobenzoic acid) self-assembles in the solid state by intermolecular hydrogen bonding to create an infinite parallel P-sheet structure. In dipeptide II Boc-gamma-Abu-m-ABA-OMe (gamma-Abu: gamma-aminobutyric acid), two such parallel beta-sheets are further cross-linked by intermolecular hydrogen bonding through m-aminobenzoic acid moieties. SEM (scanning electron microscopy) studies reveal that both the peptides I and II form amyloid-like fibrils in the solid state. The fibrils are also found to be stained readily by Congo red, a characteristic feature of the amyloid fiber whose accumulation causes several fatal diseases such as Alzheimer's, prion-protein etc.

Supramolecular helix and beta-sheet through self-assembly of two isomeric tetrapeptides in crystals and formation of filaments and ribbons in the solid state

Single crystal X-ray diffraction studies show that the beta-turn structure of tetrapeptide I, Boc-Gly-Phe-Aib-Leu-OMe (Aib: alpha-amino isobutyric acid) self-assembles to a supramolecular helix through intermolecular hydrogen bonding along the crystallographic a axis. By contrast the beta-turn structure of an isomeric tetrapeptide II, Boc-Gly-Leu-Aib-Phe-OMe self-assembles to a supramolecular beta-sheet-like structure via a two-dimensional (a, b axis) intermolecular hydrogen bonding network and pi-pi interactions. FT-IR studies of the peptides revealed that both of them form intermolecularly hydrogen bonded supramolecular structures in the solid state. Field emission scanning electron micrographs (FE-SEM) of the dried fibrous materials of the peptides show different morphologies, non-twisted filaments in case of peptide I and non-twisted filaments and ribbon-like structures in case of peptide II.

Conformational heterogeneity of tripeptides containing Boc-Leu-Aib as corner residues in the solid state

A critical analysis of single crystal X-ray diffraction studies on a series of terminally protected tripeptides containing a centrally positioned Aib (alpha-aminoisobutyric acid) residue has been reported. For the tripeptide series containing Boc-Ala-Aib as corner residues, all the reported peptides formed distorted type II beta-turn structures. Moreover, a series of Phe substituted analogues ( tripeptides with Boc-Phe-Aib) have also shown different beta-turn conformations. However, the Leu-modified analogues (tripeptides with Boc-Leu-Aib) disrupt the concept of beta-turn formation and adopt various conformations in the solid state. X-ray crystallography sheds some light on the conformational heterogeneity at atomic resolution. (c) 2007 Elsevier Ltd. All rights reserved.

Peptide mediated formation of hierarchically organized solution and solid state polymer nanostructures

Biologically-inspired peptide sequences have been explored as auxiliaries to mediate self-assembly of synthetic macromolecules into hierarchically organized solution and solid state nanostructures. Peptide sequences inspired by the coiled coil motif and "switch" peptides, which can adopt both amphiphilic alpha-helical and beta-strand conformations, were conjugated to poly(ethylene glycol) (PEG). The solution and solid state self-assembly of these materials was investigated using a variety of spectroscopic, scattering and microscopic techniques. These experiments revealed that the folding and organization properties of the peptide sequences are retained upon conjugation of PEG and that they provide the driving force for the formation of the different nanoscale structures which were observed. The possibility of using defined peptide sequences to direct structure formation of synthetic polymers together with the potential of peptide sequences to induce a specific biological response offers interesting prospects for the development of novel self-assembled and biologically active materials.

Self-assembly of beta-turn forming synthetic tripeptides into supramolecular beta-sheets and amyloid-like fibrils in the solid state

We have described here the self-assembling properties of the synthetic tripeptides Boc-Ala(1)-Aib(2) -Val (3)-OMe 1, BocAla(l)-Aib(2)-Ile(3)-OMe 2 and Boc-Ala(l)-Gly(2)-Val(3)-OMe 3 (Aib=alpha-arnino isobutyric acid, beta-Ala=beta-alanine) which have distorted beta-turn conformations in their respective crystals. These turn-forming tripeptides self-assemble to form supramolecular beta-sheet structures through intermolecular hydrogen bonding and other noncovalent interactions. The scanning electron micrographs of these peptides revealed that these compounds form amyloid-like fibrils, the causative factor for many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Prion-related encephalopathies. (C) 2004 Elsevier Ltd. All rights reserved.

Nanostructure formation in poly(gamma-benzyl-L-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl-L-glutamate) triblock copolymers in the solid state

The morphology in the solid state of a series of triblock copolymers comprising a poly(ethylene glycol) (PEG) midblock and symmetric poly(gamma-benzyl-L-glutamate) (PBLG) end blocks has been studied using X-ray scattering and microscopy techniques. Transmission electron microscopy (TEM) on samples selectively stained with uranyl acetate provided clear assignment of morphologies for as-cast and annealed samples. The thickness of both PEG and PBLG domains was in good agreement with calculations based on the conformations of the respective chains, allowing for the crystal or amorphous state of PEG and the a-helical or P-sheet structure of the PBLG. Atomic force microscopy provided complementary information on surface morphology for several samples that was in good agreement with the structure observed by TEM. A morphology diagram was constructed. Cylindrical structures were observed for ordered samples with low f(PBLG), whereas at higher f(PLBG) there was evidence for broken lamellar and "hockey puck" nanostructures. Regular lamellae were observed for intermediate compositions.

Nanozipper formation in the solid state from a self-assembling tripeptide with a single tryptophan residue

The self-assembly of a terminally protected tripeptide Boc-gamma-Abu(1)-Ala(2)-Trp(3)-OMe (gamma-Abu = gamma-aminobutyric acid) I results in the formation of a nanostructured supramolecular zipper through various non-covalent interactions in the crystal in which the indole side-chain of the Trp(3) residue plays a key role via N-H...pi interactions. (c) 2006 Published by Elsevier Ltd.

Solid-state fermentation: a continuous process for fungal tannase production

Truly continuous solid-state fermentations with operating times of 2-3 weeks were conducted in a prototype bioreactor for the production of fungal (Penicillium glabrum) tannase from a tannin-containing model substrate. Substantial quantities of the enzyme were synthesized throughout the operating periods and (imperfect) steady-state conditions seemed to be achieved soon after start-up of the fermentations. This demonstrated for the first time the possibility of conducting solid-state fermentations in the continuous mode and with a constant noninoculated feed. The operating variables and fermentation conditions in the bioreactor were sufficiently well predicted for the basic reinoculation concept to succeed. However, an incomplete understanding of the microbial mechanisms, the experimental system, and their interaction indicated the need for more research in this novel area of solid-state fermentation. (C) 2004 Wiley Periodicals, Inc.

Modelling the uptake and growth kinetics of Penicillium glabrum in a tannic acid-containing solid-state fermentation for tannase production

A mathematical growth model for the batch solid-state fermentation process for fungal tannase production was developed and tested experimentally. The unstructured model describes the uptake and growth kinetics of Penicillium glabrum in an impregnated polyurethane foam substrate system. In general, good agreement between the experimental data and model simulations was obtained. Biomass, tannase and spore production are described by logistic kinetics with a time delay between biomass production and tannase and spore formation. Possible induction mechanisms for the latter are proposed. Hydrolysis of tannic acid, the main carbon source in the substrate system, is reasonably well described with Michaelis-Menten kinetics with time-varying enzyme concentration but a more complex reaction mechanism is suspected. The metabolism of gallic acid, a tannase-hydrolysis product of tannic acid, was shown to be growth limiting during the main growth phase. (c) 2004 Elsevier Ltd. All rights reserved.

A solid-state noise source for millimetre wave spectrometry

A novel wide-band noise source for millimetre-wave spectrometry is described. It uses power combined Schottky diodes, reverse biased to avalanche breakdown, mounted in a wide-band tapered slot antenna. Power has been produced from 15 to 200 GHz with an equivalent temperature of 28200 K at 40 GHz.

Synthesis, structure and solution chemistry of dioxidovanadium(V) complexes with a family of hydrazone ligands. Evidence of formation of centrosymmetric dimers via H-bonds in the solid state

[(VO)-O-IV(acac) 2] reacts with the methanol solution of tridentate ONO donor hydrazone ligands (H2L1-4, general abbreviation H2L; are derived from the condensation of benzoyl hydrazine with 2-hydroxyacetophenone and its 5-substituted derivatives) in presence of neutral monodentate alkyl amine bases having stronger basicity than pyridine e. g., ethylamine, diethylamine, triethylamine and piperidine (general abbreviation B) to produce BH+[VO2L] (1-16) complexes. Five of these sixteen complexes are structurally characterized revealing that the vanadium is present in the anionic part of the molecule, [VO2L] in a distorted square pyramidal environment. The complexes 5, 6, 15 and 16 containing two H-atoms associated with the amine-N atom in their cationic part (e. g., diethylammonium and piperidinium ion) are involved in H-bonding with a neighboring molecule resulting in the formation of centrosymmetric dimers while the complex 12 (containing only one hydrogen atom in the cationic part) exhibits normal H-bonding. The nature of the H-bonds in each of the four centrosymmetric dimeric complexes is different. These complexes have potential catalytic activity in the aerial oxidation of L-ascorbic acid and are converted into the [VO(L)(hq)] complexes containing VO3+ motif on reaction with equimolar amount of 8-hydroxyquinoline (Hhq) in methanol.

Assessing hepatic metabolic changes during progressive colonization of germ-free mouse by 1H NMR spectroscopy

It is well known that gut bacteria contribute significantly to the host homeostasis, providing a range of benefits such as immune protection and vitamin synthesis. They also supply the host with a considerable amount of nutrients, making this ecosystem an essential metabolic organ. In the context of increasing evidence of the link between the gut flora and the metabolic syndrome, understanding the metabolic interaction between the host and its gut microbiota is becoming an important challenge of modern biology.1-4 Colonization (also referred to as normalization process) designates the establishment of micro-organisms in a former germ-free animal. While it is a natural process occurring at birth, it is also used in adult germ-free animals to control the gut floral ecosystem and further determine its impact on the host metabolism. A common procedure to control the colonization process is to use the gavage method with a single or a mixture of micro-organisms. This method results in a very quick colonization and presents the disadvantage of being extremely stressful5. It is therefore useful to minimize the stress and to obtain a slower colonization process to observe gradually the impact of bacterial establishment on the host metabolism. In this manuscript, we describe a procedure to assess the modification of hepatic metabolism during a gradual colonization process using a non-destructive metabolic profiling technique. We propose to monitor gut microbial colonization by assessing the gut microbial metabolic activity reflected by the urinary excretion of microbial co-metabolites by 1H NMR-based metabolic profiling. This allows an appreciation of the stability of gut microbial activity beyond the stable establishment of the gut microbial ecosystem usually assessed by monitoring fecal bacteria by DGGE (denaturing gradient gel electrophoresis).6 The colonization takes place in a conventional open environment and is initiated by a dirty litter soiled by conventional animals, which will serve as controls. Rodents being coprophagous animals, this ensures a homogenous colonization as previously described.7 Hepatic metabolic profiling is measured directly from an intact liver biopsy using 1H High Resolution Magic Angle Spinning NMR spectroscopy. This semi-quantitative technique offers a quick way to assess, without damaging the cell structure, the major metabolites such as triglycerides, glucose and glycogen in order to further estimate the complex interaction between the colonization process and the hepatic metabolism7-10. This method can also be applied to any tissue biopsy11,12.