Theoretical studies on the conformations of higher gangliosides

The possible conformations of higher gangliosides (GD3, GT1a. GT1b, GQ1b) have been determined by computing their potential energy using semi-empirical potential functions. The favoured conformation of the disialic acid fragment in these gangliosides is independent of its position (internal or terminal). The favoured conformations of these gangliosides have also been correlated to their biological activity. The results suggest that tetanus toxin and sendai virus may have a large binding site which can accommodate at least four sugar residues.

Conformations of lasalocid A-lithium complexes in acetonitrile

The interaction of the ionophore antibiotic lasalocid-A with lithium perchlorate in acetonitrile has been studied by circular dichroism (c.d.) and 1H, 13C and 7Li nuclear magnetic resonance (n.m.r.) techniques. Analysis of the c.d. data has shown that both the 2:1 sandwich (ionophore-cation-ionosphore) complex and 1:1 complex coexist in solution. The n.m.r. data are consistent with a conformational model in which the carbonyl oxygen, he tetrahydrofuran and the tetrahydropyran ring oxygen atoms, two hydroxyl group oxygens and either a water or a solvent molecule coordinate to the lithium ion.

Alamethicin and synthetic peptide fragments as uncouplers of mitochondrial oxidative phosphorylation. Effect of chain length and change

Alamethicin, its derivatives and some synthetic fragments have been shown to be uncouplers of oxidative phosphorylation in rat liver mitochondria. A minimum peptide chain length of 13 residues is necessary for this activity. Peptide esters are more efficient uncouplers than the corresponding peptide acids. Esterification of the Glu(18) γ-COOH group in alamethicin does not diminish uncoupling activity. The structural requirements for uncoupling activity parallel those determined for ionophoretic action in small, unilamellar liposomes. Aib, α-aminoisobutyric acid; Z, benzyloxycarbonyl; OMe, methyl ester; OBz, benzyl ester; Ac, acetyl; CTC, chlortetracycline.

Acyclic peptides as conformational models Crystal structure of Boc-Aib-Leu-Pro-NHMe± 2H2O

The tripeptide Boc-Aib-Leu-Pro-NHMe crystallizes in the orthorhombic space group P212121 with a = 9.542, b = 15.200, c = 18.256 Å and Z = 4. Each peptide is associated wth two water molecules in the asymmetric unit of the crystal. The structure has been solved by direct methods and refined to an R-value of 0.069. The peptide adopts a structure without any intramolecular hydrogen bond. The three residues occupy distinctly different regions of the Ramachandran map: Aib in the left-handed 310-helical region (± = 67°, ± = 23°), Leu in the β-sheet region (± = - 133°, ± = 142°) and Pro in the poly (Pro) II region (± = - 69°, ± = 151°). An interesting observation is that each water molecule participates in four hydrogen bonds with distorted tetrahedral coordination about the oxygen atom.

Fluorescence And Nmr-Studies Of The Binding Of Cholinergic Fluorescent-Probes To Horse Serum-Cholinesterase

The interaction of the cholinergic fluorescent probes, 1-(5-dimethyl-aminoaphthalene-1-sulfonamido) ethane-2-trimethylammonium perchlorate, 1-(5-dimethylaminonaphthalene-1-sulfonamido) pentane-5-trimethylammonium tartarate and 1-(5-dimethylaminonaphthalene-1-sulfonamido) decane-10- trimethylammonium tartarate with horse serum cholinesterase has been examined by fluorescence and n.m.r. methods. Fluorescence titrations show binding of the decane derivative to two sites on the protein whereas the lower homologs bind largely to one site. Active site inhibitors like curbamylcholine and decamethonium abolish binding of the decane derivative to the high affinity site. The inhibitors are largely without effect on the binding of the lower homologs. N.m.r. studies clearly establish immobilization of both ends of the molecule on binding in the case of the decane derivative, whereas in the lower homologs the dimethylamino group on the naphthalene ring is significantly more affected in the presence of enzyme. The probes are effective inhibitors of the enzyme with the decane derivative being two orders of magnitude more effective than its lower homologs. Based on the n.m.r., fluorescence and inhibition studies, a model for probe binding to the enzyme is advanced. It appears that the decane derivative binds with high affinity to the catalytic anionic site while the lower affinity site is assigned to a peripheral anionic site. The lower homologs probe only the peripheral site. A comparison of fluorescence, n.m.r. and inhibition studies with acetylcholinesterases from electric eel and bovine erythrocytes is presented.

Preferred conformations and flexibility of aminoacyl side chain of penicillins

Possible conformations of penicillin G; d and l isomers of ampicillin; α-amino-α-methyl-benzyl penicillins and 3- pyridyl methyl penicillin have been studied by an energy minimization procedure using empirical potential functions. The preferred conformations of these antibiotics have been correlated with their biological activity. The conformational requirement of the antibiotic to be active against Gram-positive and Gram-negative (β-lactamase-negative) bacterial strains seems to be the same. The reduced activity of penicillin G against Gram-negative bacteria has been attributed to its lower ability to permeate the outer membrane. The flexibility of the sidechains of these antibiotics is also shown to be important for the desired biological activity.

Regional differentiation in bull sperm plasma-membranes

Bull sperm heads and tails have been separated by proteolytic digestion (trypsin) and plasma membranes have been isolated, using discontinuous sucrose density gradient centrifugation. Plasma membrane bound Ca2+-ATPase is shown to be associated mostly with the tail membranes. Pyrene excimer fluorescence and diphenylhexatriene fluorescence polarization experiments indicate a more fluid lipid phase in the tail region. Differences in surface charge distribution have been found, using 1-anilinonaphthalene-8-sulfonate and Tb3+ as fluorescent probes.

Thermodynamic and kinetic studies on saccharide binding to soya-bean agglutinin.

The fluorescence of N-dansylgalactosamine [N-(5-dimethylaminonaphthalene-1-sulphonyl)galactosamine] was enhanced 11-fold with a 25 nm blue-shift in the emission maximum upon binding to soya-bean agglutinin (SBA). This change was used to determine the association constants and thermodynamic parameters for this interaction. The association constant of 1.51 X 10(6) M-1 at 20 degrees C indicated a very strong binding, which is mainly due to a relatively small entropy value, as revealed by the thermodynamic parameters: delta G = -34.7 kJ X mol-1, delta H = -37.9 kJ X mol-1 and delta S = -10.9 J X mol-1 X K-1. The specific binding of this sugar to SBA shows that the lectin can accommodate a large hydrophobic substituent on the C-2 of galactose. Binding of non-fluorescent ligands, studied by monitoring the fluorescence changes when they are added to a mixture of SBA and N-dansylgalactosamine, indicates that a hydrophobic substituent at the anomeric position increases the affinity of the interaction. The C-6 hydroxy group also stabilizes the binding considerably. Kinetics of binding of N-dansylgalactosamine to SBA studied by stopped-flow spectrofluorimetry are consistent with a single-step mechanism and yielded k+1 = 2.4 X 10(5) M-1 X s-1 and k-1 = 0.2 s-1 at 20 degrees C. The activation parameters indicate an enthalpicly controlled association process.

Chemical Modification Studies On Ricinus-Communis (Castor Bean) Agglutinin

Ricinus communis agglutinin was subjected to various chemical treatments and the effect on its hemagglutinating and saccharide-binding properties was studied. Acetylation, succinylation and citraconylation led to a complete loss in the activity of the agglutinin, whereas reductive methylation had no effect on the activity, showing that charged amino groups were involved in the hemagglutinating and saccharide-binding activity of Ricinus agglutinin. Modification of tryptophyl, arginyl and carboxyl-group-containing residues did not lead to any loss in the activity of the agglutinin. Acetylation of tyrosyl groups with N-acetylimidazole strongly reduced the hemagglutinating and saccharide-binding property of Ricinus agglutinin. The loss in activity was restored on deacetylation of the tyrosyl groups. Modification of tyrosyl residues also led to a change in the immunological properties of the agglutinin. The initial rate of modification of tyrosyl and amino groups and the concomitant loss of activity was reduced in the presence of lactose.

Flexibility of the furanose ring in nucleic acids: a compilation of crystal data

A compilation of crystal structure data on deoxyribo- and ribonucleosides and their higher derivatives is presented. The aim of this paper is to highlight the flexibility of deoxyribose and ribose rings. So far, the conformational parameters of nucleic acids constituents of ribose and deoxyribose have not been analysed separately. This paper aims to correlate the conformational parameters with the nature and puckering of the sugar. Deoxyribose puckering occurs in the C2′ endo region while ribose puckering is observed both in the C3′ endo and C2′ endo regions. A few endocyclic and exocyclic bond angles depend on the puckering and the nature of the sugar. The majority of structures have an anti conformation about the glycosyl bond. There appears to be a puckering dependence on the torsion angle about the C4′---C5′ bonds. Such stereochemical information is useful in model building studies of polynucleotides and nucleic acids.

X-Pro peptides. A theoretical study of the hydrogen bonded conformations of (alpha-aminoisobutyryl-L -prolyl)n sequences

Intramolecularly hydrogen bonded conformations of (Aib-Pro)n sequences have been analysed theoretically. Both 4-1 (C10 and 3-1 (C7 hydrogen bonded regular structures are shown to be stereochemically feasible. Conformational energies for the helical structures have been estimated using classical potential energy methods. Both C10 and C7 conformations have very similar energies. Pyrrolidine ring puckering has a pronounced effect on the energies, and only Cv-endo puckered Pro residues can be accommodated. The theoretical calculations using spectroscopic data suggest that the recently proposed novel 310 helical conformation for benzyloxycarbonyl(Aib-Pro)4-methyl ester is in solution, is indeed energetically and stereochemically favourable.

N-Acetylglycyl-L-lysine methyl ester acetate

C llH22 N 30 + . C2H302, orthorhombic, P2~2~2~, a = 5.511(2), b = 14.588(4), c = 21.109 (4)A, Z = 4. The structure has been solved using MULTAN and refined to R = 0.079 for 993 observed reflections. The fully extended lysine side chain in the molecule is staggered between the main-chain amino and carbonyl groups. The dipeptide molecules in the crystal structure are arranged in twofold helices centred on 21 screw axes. These helices are interconnected through interactions involving the acetate and the side-chain amino groups. Each acetate group bridges two adjacent side-chain amino groups, related by an a translation, giving rise to an infinitely long chain of alternating negatively charged carboxylate and positively charged amino groups.

Structure of a new crystal form of 2- ([3-(trifluoromethyl)phenyl] amino)benzoic acid (flufenamic acid)

C14Ht0F3NO2, P2.Jc, a = 12.523 (4), b = 7.868(6), c = 12.874 (3)A, fl = 95.2 (2) ° , O,,, = 1.47 (4), D e = 1.47 Mg m -3, Z = 4. Final R = 0.074 for 2255 observed reflections. The carboxyl group and the phenyl ring bearing the carboxyl group are nearly coplanar whereas the two phenyl rings are inclined with respect to each other at 52.8 ° . The difference between the two polymorphs of flufenamic acid lies in the geometrical disposition of the [3-(trifluoromethyl)- phenyl]amino moiety with respect to the benzoic acid moiety. As in other fenamate structures, the carboxyl group and the imino N atom are connected through an intramolecular hydrogen bond; also, pairs of centrosymmetrically related molecules are connected through hydrogen bonds involving carboxyl groups.