Hydration and distortion of peptide helices in crystals. α-Helical structure of a dodecapeptide, Boc-(Ala-Leu-Aib)4-OMe

The dodecapeptide Boc-(Ala-Leu-Aib)(4)-OMe crystallized with two independent helical molecules in a triclinic cell. The two molecules are very similar in conformation, with a 3(10)-helix turn at the N-terminus followed by an alpha-helix, except for an elongated N(7)...O(3) distance in both molecules. All the helices in the crystal pack in a parallel motif. Eleven water sites have been found in the head-to-tail region between the apolar helices that participate in peptide-water hydrogen bonds and a network of water-water hydrogen bonds. The crystal parameters are as follows: 2(C58H104N12O15)+ca. 10H(2)O, space group P1 with a = 12.946(2), b = 17.321(3), c = 20.465(4) Angstrom, alpha = 103.12(2), beta = 105.63(2), gamma = 107.50(2)degrees, Z = 2, R = 10.9% for 5152 data observed > 3 sigma(F), resolution 1.0 Angstrom. In contrast to the shorter sequences [Karle et al. (1988)Proc. Natl. Acad. Sci. USA 85, 299-303] and Boc-(Ala-Leu-Aib)(2)-OMe [Karle et al. (1989) Biopolymers 28, 773-781], no insertion of a water molecule into the helix is observed. However, the elongated N---O distance between Ala(7) NH and Aib(3) CO in both molecules (molecule A, 3.40 Angstrom; molecule B, 3.42 Angstrom) is indicative of an incipient break in the helices. (C) Munksgaard 1994.

Stereochemical Analysis of Higher α,α-Dialkylglycine Containing Peptides. Characterization of Local Helical Conformations at Dipropylglycine Residues and Observation of a Novel Hydrated Multiple β-Turn Structure in Crystals of a Glycine Rich Peptide

The peptide Boc-Gly-Dpg-Gly-Gly-Dpg-Gly-NHMe (1) has been synthesized to examine the conformational preferences of Dpg residues in the context of a poor helix promoting sequence. Single crystals of 1 were obtained in the space group P21/c with a = 13.716(2) Å, b = 12.960(2) Å, c = 22.266(4) Å, and β = 98.05(1)°; R = 6.3% for 3660 data with |Fo| > 4σ. The molecular conformation in crystals revealed that the Gly(1)-Dpg(2) segment adopts φ, ψ values distorted from those expected for an ideal type II‘ β-turn (φGly(1) = +72.0°, ψGly(1) = −166.0°; φDpg(2) = −54.0°, ψDpg(2) = −46.0°) with an inserted water molecule between Boc-CO and Gly(3)NH. The Gly(3)-Gly(4) segment adopts φ, ψ values which lie broadly in the right handed helical region (φGly(3) = −78.0°, ψGly(3) = −9.0°; φGly(4) = −80.0°, ψGly(4) = −18.0°). There is a chiral reversal at Dpg(5) which takes up φ, ψ values in the left handed helical region. The Dpg(5)-Gly(6) segment closely resembles an ideal type I‘ β-turn (φDpg(5) = +56.0°, ψDpg(5) = +32.0°; φGly(6) = +85.0°, ψGly(6) = −3.0°). Molecules of both chiral senses are found in the centrosymmetric crystal. The C-terminus forms a hydrated Schellman motif, with water insertion into the potential 6 → 1 hydrogen bond between Gly(1)CO and Gly(6)NH. NMR studies in CDCl3 suggest substantial retention of the multiple turn conformation observed in crystals. In solution the observed NOEs support local helical conformation at the two Dpg residues.

Excited-state structures of molecules with nearby electronic states

Vibronic coupling among the nearby excited electronic states via the in-plane and the out-of-plane nuclear motions is examined in benzene, pyrazine, formaldehyde and thioformaldehyde. Results reveal that in benzene the structure distorts via the most active nuclear bending (planar) motion while in the other molecules the structures distort through an out-of-plane bending motion in their respective lowest excited states.

Effect of coordinated ions on structure and flexibility of parallel G-quadruplexes: A molecular dynamics study

ingle tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G(7)) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the O6 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. There quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 Angstrom from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Nai counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. in the absence of any coordinated ion. due to strong mutual repulsion, O6 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures.

Enantiodiscrimination and extraction of short and long range homo- and hetero-nuclear residual dipolar couplings by a spin selective correlation experiment

A two dimensional correlation experiment for the measurement of short and long range homo- and hetero- nuclear residual dipolar couplings (RDCs) from the broad and featureless proton NMR spectra including C-13 satellites is proposed. The method employs a single natural abundant C-13 spin as a spy nucleus to probe all the coupled protons and permits the determination of RDCs of negligible strengths. The technique has been demonstrated for the study of organic chiral molecules aligned in chiral liquid crystal, where additional challenge is to unravel the overlapped spectrum of enantiomers. The significant advantage of the method is demonstrated in better chiral discrimination using homonuclear RDCs as additional parameters. (C) 2010 Elsevier B.V. All rights reserved.

Structural studies of analgesics and their interactions. XII. Structure and interactions of anti-inflammatory fenamates. A concerted crystallographic and theoretical conformational study

A theoretical conformational analysis of fenamates, which are N-arylated derivatives of anthranilic acid or 2-aminonicotinic acid with different substituents on the aryl (phenyl) group, is reported. The analysis of these analgesics, which are believed to act through the inhibition of prostaglandin biosynthesis, was carried out using semi-empirical potential functions. The results and available crystallographic observations have been critically examined in terms of their relevance to drug action. Crystallographic studies of these drugs and their complexes have revealed that the fenamate molecules share a striking invariant feature, namely, the sixmembered ring bearing the carboxyl group is coplanar with the carboxyl group and the bridging imino group,the coplanarity being stabilized by resonance interactions and an internal hydrogen bond between the imino and carboxyl groups. The results of the theoretical analysis provide a conformational rationale for the observed invariant coplanarity. The second sixmembered ring, which provides hydrophobicity in a substantial part of the molecule, has limited conformational flexibility in meclofenamic, mefenamic and flufenamic acids. Comparison of the conformational energy maps of these acids shows that they could all assume the same conformation when bound to the relevant enzyme. The present study provides a structural explanation for the difference in the activity of niflumic acid, which can assume a conformation in which the whole molecule is nearly planar. The main role of the carboxyl group appears to be to provide a site for intermolecular interactions in addition to helping in stabilizing the invariant coplanar feature and providing hydrophilicity at one end of the molecule. The fenamates thus provide a good example of conformation- dependent molecular asymmetry.

Structure of 6-acetoxycoumarin: topochemical photodimerization and analysis of acetoxy...acetoxy interactions in the solid state

C~HaO 4, Mr=204.2, monoclinic, P2Jn,a=3.900(1), =37.530(6), c=6.460(1)A, fl=103.7 (1) °, V= 918.5 (5) A 3, Z = 4, D m = 1.443, D x --- 1.476 Mg m -3, Cu Ks, 2 = 1.5418 ,/k, /t = 0.86 mm -~, F(000) = 424, T= 293 K, R = 0.075 for 1019 significant reflections. Molecules pack in fl-type stacking mode which is characterized by the close packing of parallel and nearly planar reactive double bonds with a separation of 3.900/~ along the a axis.The syn head-head dimer obtained is the direct consequence of this packing arrangement. Molecular packing is stabilized by intermolecular C-H...O hydrogen bonding. Analysis of acetoxy...acetoxy interactions in the acetoxy compounds retrieved from the Cambridge Structural Database reveal that the majority of them are anti-dipolar.

Differences in hydration and association of helical Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-(Val-Ala-Leu-Aib)2-OMe. xH2O in two crystalline polymorphs

The 15-residue apolar peptide, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-(Val-Ala-Leu-Aib)h2a-sO Mebeen crystallized from 2-propanol-water (form I). The crystal parameters for I are as follows:C74H133N15018*2H20s,p ace group P21, a = 9.185 (6) A, b = 47.410 (3) A, c = 10.325 (9) A, @ = 91.47(2)O, 2 = 2, R = 6.3% for 4532 reflections observed >3aQ, resolution 0.94 A. The structure isalmost completely a-helical with eleven 5-1 hydrogen bonds and one 441 hydrogen bond nearthe N-terminus. The structure has been compared with a polymorph (form 11) obtained frommethanol-water (Karle, I. L.; Flippen-Anderson, J. L.; Uma, K.; Sukumar, M.; Balaram, P., J. An.Chem. SOC19. 90,112,9350-9356). The two forms differ in the extent of hydration; form I contains two water molecules in the head-to-tail region of helical columns, while form I1 is more extensively solvated, with the equivalent of 7.5 water molecules. The three-dimensional packing of helices is completely parallel in I and antiparallel in 11.

Design and fabrication of an indigenous molecular beam ultraviolet photoelectron spectrometer

An ultraviolet photoelectron spectrometer for the study of van der Waals molecules has been designed and fabricated indigenously. The spectrometer consists of an HeI discharge lamp, a molecular beam sample inlet system, an electrostatic lens, a 180-degrees hemispherical electrostatic analyser and a channeltron detector. Performance of the spectrometer is illustrated with an example.

Preparation and characterization of immunoliposomes for targeting of antiviral agents

Antibodies specific to avian myeloblastosis virus envelope glycoprotein gp80 were raised. Immunoliposomes were prepared using anti-avian myeloblastosis virus envelope glycoprotein gp80 antibody. The antibody was palmitoylated to facilitate its incorporation into lipid bilayers of liposomes. The fluorescence emission spectra of palmitoylated IgG have exhibited a shift in emission maximum from 330 to 370 nm when it was incorporated into the liposomes. At least 50% of the incorporated antibody molecules were found to be oriented towards the outside in the liposomes. The average size of the liposome was found to be 300 A, and on an average, 15 antibody molecules were shown to be present in a liposome. When adriamycin encapsulated in immunoliposomes was incubated in a medium containing serum for 72 h, about 75% of the drug was retained in liposomes. In vivo localization studies, revealed an enhanced delivery of drug encapsulated in immunoliposomes to the target tissue, as compared to free drug or drug encapsulated in free liposomes. These data suggest a possible use of the drugs encapsulated in immunoliposomes to deliver the drugs in target areas, thereby reducing side effects caused by antiviral agents.

Spectroscopic properties of molecules related to hindered isomers of retinal

Proton and12C NMR study of molecules related to retinal has been carried out. The characteristic differences in spectral behaviour among 7-trans and 7-cis isomers have been established which would be useful in determining the structure of new isomers and identifying components in a mixture. Through coupling constant measurements and DNMR study it is clearly established that 7-cis isomers of β-ionyl derivatives and in turn 7-cis isomers of retinyl derivatives prefer a non-planar arrangement and this non-planarity brings about resonance destabilisation.

The influence of chemical additives on surface charge and hardness of hematite

The zeta potential of high-purity hematite at pH 6 and in a 10−3N NaCl solution has been determined at different concentrations of acetone using the streaming potential technique and the results correlated with the microhardness of the mineral. The zeta potential has been found to decrease as the hardness increases reaching a minimum at 10 cc per litre concentration of acetone when the hardness reaches a maximum. The results have been explained on the basis of competitive adsorption of chloride ions and acetone molecules at low concentrations of acetone and coadsorption of both species above 10 cc per litre concentration. Acetone in distilled water and 10−3N NaCl in distilled water decrease the microhardness of hematite individually between pH 5 to 7 and in combination increase the microhardness reaching a maximum at pH 6.

Entropy and dynamics of water in hydration layers of a bilayer

We compute the entropy and transport properties of water in the hydration layer of dipalmitoylphosphatidylcholine bilayer by using a recently developed theoretical scheme two-phase thermodynamic model, termed as 2PT method; S.-T. Lin et al., J. Chem. Phys. 119, 11792 (2003)] based on the translational and rotational velocity autocorrelation functions and their power spectra. The weights of translational and rotational power spectra shift from higher to lower frequency as one goes from the bilayer interface to the bulk. Water molecules near the bilayer head groups have substantially lower entropy (48.36 J/mol/K) than water molecules in the intermediate region (51.36 J/mol/K), which have again lower entropy than the molecules (60.52 J/mol/K) in bulk. Thus, the entropic contribution to the free energy change (T Delta S) of transferring an interface water molecule to the bulk is 3.65 kJ/mol and of transferring intermediate water to the bulk is 2.75 kJ/mol at 300 K, which is to be compared with 6.03 kJ/mol for melting of ice at 273 K. The translational diffusion of water in the vicinity of the head groups is found to be in a subdiffusive regime and the rotational diffusion constant increases going away from the interface. This behavior is supported by the slower reorientational relaxation of the dipole vector and OH bond vector of interfacial water. The ratio of reorientational relaxation time for Legendre polynomials of order 1 and 2 is approximately 2 for interface, intermediate, and bulk water, indicating the presence of jump dynamics in these water molecules. (C) 2010 American Institute of Physics. doi:10.1063/1.3494115]

Visualization of enantiomers and determination of homo- and hetero-nuclear residual dipolar and scalar couplings: The natural abundant C-13 edited J/D-resolved NMR techniques

The simple two dimensional C-13-satellite J/D-resolved experiments have been proposed for the visualization of enantiomers, extraction of homo- and hetero-nuclear residual dipolar couplings and also H-1 chemical shift differences between the enantiomers in the anisotropic medium. The significant advantages of the techniques are in the determination of scalar couplings of bigger organic molecules. The scalar couplings specific to a second abundant spin such as F-19 can be selectively extracted from the severely overlapped spectrum. The methodologies are demonstrated on a chiral molecule aligned in the chiral liquid crystal medium and two different organic molecules in the isotropic solutions. (C) 2010 Elsevier B.V. All rights reserved.

Hollow hemisphere and microcapsules of nonionic copolymer

Hemispherical colloidal nanowells or microwells with hollow interiors are becoming increasingly important for the encapsulation of functional materials. There has been rapid progress to develop new methods to obtain such structures. In this work, we present emulsification approach to generate hemisphere and microcapsules of biocompatible organic polymer. The precise control over the size is exhibited by applying variable vortex effect. The hemispheres and microcapsules of a copolymer (BPVA-PVA) were characterized by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). These structures were used for loading of hydrophilic molecules and submicron colloidal particles to demonstrate their potential application. The introduction of hydrophobic groups on poly(vinyl alcohol) was crucial to obtain these structures.