Effects of membrane channel-forming polypeptides on mitochondrial oxidative phosphorylation. A comparison of alamethicin, gramicidin A, melittin and tetraacetyl melittin.

Transmembrane channel-forming polypeptides can function as uncouplers of mitochondrial oxidative phosphorylation. The observed effects are dependent on the phosphate ion (Pi) concentration in the medium. At low Pi (2.5 mM) the order of uncoupling efficiencies is gramicidin A much greater than alamethicin greater than tetraacetyl melittin greater than melittin. The remarkably high activity of gramicidin A suggests insertion of preformed channel dimers into the membrane. It is also suggested that lipid phase association of peptides is necessary in the other cases. At Pi = 100 mM inhibitory effects are observed for alamethicin and tetraacetyl melittin. Less pronounced inhibition is seen for melittin, while no such effect is noted for gramicidin A. The site of inhibition is shown to be complex IV, and the differences in the behavior of the peptides are rationalized in terms of channel structures.

A theory on the migration of an extraneous electron across hydrogen bonds in polypeptides

The migrating electrons in biological systems normally are extraneous and taking this into account the electron delocalisation across the hydrogen bonds in proteins is re-examined. It is seen that an extraneous electron can travel rapidly via the low-lying virtual orbitals of the hydrogen-bonded π-electronic structure of peptide units in proteins. The frequency of electron transfer decreases slowly with an increase in the path length. However, the coupling of electron and protonic motions enhances this frequency. Transfer of electrons across the hydrogen bonds in accordance with the double-exchange mechanism does not appear to be possible. This theory offers a possibility for an extraneous electron to transfer within protein structures.

A formate bridged Ni(II) sheet and its 3D analogue in presence of a linear organic linker: Synthesis, crystal structure and magnetic properties

Reaction of formamide with Ni(NO3)(2)center dot 6H(2)O under hydrothermal condition in a mixture of MeOH/H2O forms a two-dimensional formate bridged sheet Ni(HCOO)(2)(MeOH)(2) (1). X-ray structure analysis reveals the conversion of formamide to formate which acts as a bridging ligand in complex 1 where the axial sites of Ni(II) are occupied by methanol used as a solvent. An analogous reaction in presence of 4,4'-bipyridyl (4,4'-bipy) yielded a three-dimensional structure Ni(HCOO)(2)(4,4'-bpy) (2). DC magnetic measurements as a function of temperature and field established the presence of spontaneous magnetization with T-c (Curie temperature) = 17 and 20.8 K in 1 and 2, respectively, which can be attributed due to spin-canting. DFT calculations were performed to corroborate the magnetic results of 1 and 2. (C) 2010 Elsevier Ltd. All rights reserved.

Fourfold Helical Structures for Polypeptides

Fourfold helical structures for polypeptides and their association in regular lattices with interchain hydrogen bonds were investigated by model building studies. These studies revealed that stereochemically satisfactory fourfold helical sturctures are possible for polyglycine, polyproline, and copolymers of glycine and proline with two and four units in the monomer. In these structures the unit height h for the backbone has been found to be restricted from 2.7 to 3.1 k, with four peptide units per turn of the helix. Energetically both fourfold and threefold helical structures are equally favorable.

Modelling multiple disulphide loop containing polypeptides by random conformation generation. The test cases of α-conotoxin GI and edothelin I

A general procedure for arriving at 3-D models of disulphiderich olypeptide systems based on the covalent cross-link constraints has been developed. The procedure, which has been coded as a computer program, RANMOD, assigns a large number of random, permitted backbone conformations to the polypeptide and identifies stereochemically acceptable structures as plausible models based on strainless disulphide bridge modelling. Disulphide bond modelling is performed using the procedure MODIP developed earlier, in connection with the choice of suitable sites where disulphide bonds could be engineered in proteins (Sowdhamini,R., Srinivasan,N., Shoichet,B., Santi,D.V., Ramakrishnan,C. and Balaram,P. (1989) Protein Engng, 3, 95-103). The method RANMOD has been tested on small disulphide loops and the structures compared against preferred backbone conformations derived from an analysis of putative disulphide subdatabase and model calculations. RANMOD has been applied to disulphiderich peptides and found to give rise to several stereochemically acceptable structures. The results obtained on the modelling of two test cases, a-conotoxin GI and endothelin I, are presented. Available NMR data suggest that such small systems exhibit conformational heterogeneity in solution. Hence, this approach for obtaining several distinct models is particularly attractive for the study of conformational excursions.

Hybrid Polypeptides: Gabapentin as a Stereochemically Constrained gamma-Amino Acid Residue

The design of folded structures in peptides containing the higher homologues of alpha-amino acid residues requires the restriction of the range of local conformational choices In alpha-amino acids stereochemically constrained residues like alpha,alpha-dialkylated residue, aminoisobutyric acid (Aib), and D-Proline ((D)Pro) have proved extremely useful in the design of helices and hairpins in short peptides Extending this approach, backbone substitution and cyclization are anticipated to bc useful in generating conformationally constrained beta- and gamma-residues This brief review provides a survey of work on hybrid peptide sequences concerning the conformationally constrained gamma-amino acid residue 1-aminomethyl cyclohexane acetic acid, gabapentin (Gpn) This achiral, beta,beta-disubstituted, gamma-residue strongly favors gauche-gauche conformations about the C-alpha-C-beta (0(2)) and C-alpha-C-gamma (0(1)) bonds, facilitating local folding The Gpn residue can adopt both C-7 (NH1 -> CO1) and C-9 (CO1 (I)<- NH1+I) hydrogen bonds which are analogous to the C-5 and C7 (gamma-turn) conformations at alpha-residues In conjunction with adjacent residues, Gpn may be used in ay and gamma alpha segments to generate C-12 hydrogen bonded conformations which may be considered as expanded analogs of conventional beta-turns The structural characterization of C-12 helices, C-12/C-10 helices with mixed hydrogen bond directionalities and beta-hairpins incorporating Gpn residues at the turn segment is illustrated (C) 2010 Wiley Periodicals, Inc Biopolymers (Pept Sci) 94 733-741 2010

Synthesis, glucose uptake activity and structure-activity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker

Three series of novel glitazones were designed and prepared by using appropriate synthetic schemes to incorporate glycine, aromatic and alicyclic amines via two carbon linker. Compounds were synthesized both under conventional and microwave methods. Nineteen out of twenty four synthesized compounds were evaluated for their in vitro glucose uptake activity using isolated rat hemi-diaphragm. Compounds, 6, 9a, 13a, 13b, 13c, 13f and 13h exhibited significant glucose uptake activity. Illustration about their synthesis and in vitro glucose uptake activity is described along with the structure activity relationships. (C) 2010 Elsevier Masson SAS. All rights reserved.

Beta-structure of polypeptides in non-aqueous solutions. I. Spectral characteristics of the polypeptide backbone

The optical rotatory features of the beta-structure of the polypeptides in non-aqueous solutions and films cast from these solutions have been investigated. The beta-structure of poly-S-benzyl-L-cysteine, poly-S-carbobenzoxy-L-cysteine and poly-S-benzyl-L-cysteine, poly-S-carbobenzoxy-L-cysteine and poly-O-carbo-bands of their films. The optical rotatory dispersion (ORD) and circular dichroism (CD) spectra of these polypeptides are found to be very similar in both film and solution. In solvents promoting the beta-structure, the polypeptides are characterized by CD troughs in the n-pi* transition region of the peptide chromophore. The ORD spectra are found to be positive in sign throughout the visible and accessible ultraviolet regions and are interpreted in terms of the possible existence of a relatively much larger positive pi-pi* CD bands as compared with the negative n-pi* band. The rotatory data obtained in the non-aqueous solution are compared with those obtained for other poly peptides in aqueous solutions, with respect to the type and extent of beta-structure present.

Beta-structure of polypeptides in non-aqueous solutions. II. Side-chain orientation

The specific side-chain orientations of the phenyl group in the polypeptides poly-S-benzyl-L-cysteine, poly-S-carbobenzoxy-L-cysteine and poly-O-carbobenzoxy-L-serine in the beta-structure have been studied by spectral measurements in solutions. All the three polypeptides exhibit aromatic CD bands, indicating the asymmetric placement of the side-chain phenyl rings when the polypeptide backbone takes up the antiparallel beta-structure. Supporting evidence for this is derived from n.m.r. spectra of the polypeptides, which show upfield shift of the phenyl protons due to the stacking of the aromatic rings. Molecular model building studies reveal the stacking of alternate phenyl groups along the polypeptide chain.