通光藤甙F,G,H和I结构

从通光藤(Marsdeniatenacissima)的茎中分离得到4个新的C21甾体甙———通光藤甙F(3),G(4),H(5)和I(6),以及2个已知化合物通光藤甙A(1)和B(2)。根据光谱数据和化学方法推定了其结构。同时,通过COLOC谱和二维核磁共振谱指定了这些化合物中甙元上11和12位的酯基确切连接位置。     

Molecular Mechanics and Dynamics of an Abasic Frameshift in DNA and Comparison to NMR Data

Abstract

In a previous publication (Ph. Cuniasse, L.C. Sowers, R. Eritja, B. Kaplan, M.F. Goodman, J.A.H. Cognet, M. Le Bret, W. Guschlbauer and G.V. Fazakerley, Biochemistry 28, 2018 (1989), we determined by two dimensional NMR studies and molecular mechanics calculations the three-dimensional structure of a non-selfcomplementary oligonucleotide:

5′d(C1 P1 G2 P2 G3 P3 dr4 P4 G5 P5 G6 P6 C7)3′

3′d(G13P12C12PllCll P10 C10 P9 C9 P8 G8)5′

where dr, at the center of the first strand, is a model abasic site. In order to explain all the results arising from NMR measurements, we found that an equilibrium between two conformations was necessary. These conformations differ mainly by the sugar pucker of G5 which is C2′ endo or C3′ endo. The latter is stabilized by addition of counterions between phosphate residues P3 and P4.

In this paper, we have constructed systematically, all possible structures as a function of torsion angles delta of dr4 and of G5 by molecular mechanics in the presence or absence of counterions. Since these conformations were not forced with NMR distance measurements, this method allows detailed comparisons between all possible conformations and NMR data. Maps of contour lines of the potential energy, of fits to NMR distance measurements, and of helical twist as a function of torsion angles delta of dr4 and of G5 unravel the difficulties associated with the study of the G5 sugar pucker conformation equilibrium.

Sugar puckers and proton distances are very sensitive criteria to monitor molecular dynamics. Relying on these experimental criteria, we have tested many molecular dynamics preparation phases and we propose a new warm-up and equilibration procedure for molecular dynamics. Thus we show with a 290 ps molecular dynamic run that G5 is in conformational equilibrium and that all NMR data are well reproduced.     

Epitope scanning reveals gain and loss of strain specific antibody binding epitopes associated with the conversion of normal cellular prion to scrapie prion

We used anti-prion (PrP) monoclonal antibodies (Mabs) in different combinations to scan changes in the availability of antibody binding epitopes--using an epitope scanning assay--in brain homogenates from normal mice, and from mice infected with either ME7 or 139 A strains of infectious scrapie prion (PrPSc). In ME7-infected brains, the epitope detected by the Mab pair 8B4/8H4 is reduced, while the epitope detected by the Mab pair 8F9/11G5 is increased. Mab 8F9/11G5 detect a conformational epitope on PrPSc because the rise in Mab 8F9/11G5 binding is sensitive to a denaturing agent but resistant to proteinase K (PK). While the increase in Mab 8F9/11G5 binding correlates with the presence of PK-resistant PrP and clinical signs of infection, the reduction in Mab 8B4/8H4 binding is detected earlier. Fractionation of the ME7-infected brain homogenate in sucrose gradient revealed that the PrPSc species detected by the epitope scanning assay are heterogeneous in size, with a molecular mass of approximately > or = 2000-kDa. We also investigated whether these findings were applicable to two other strains of PrPSc, namely 87 V and 22 L. We found that the decrease in Mab 8B4/8H4 binding detected in ME7-infected brains was also detected in 87 V-infected brains but not in 22 L-infected brains. In contrast, the increase in Mab 8F9/11G5 binding detected in ME7- and 139 A-infected brains was also detected in 22 L-infected brains but not in 87 V-infected brains. Therefore, each prion strain has its unique conformation, and we can monitor the conversion of normal cellular prion (PrPC) to PrPSc based on the changes in the antibody binding patterns. The epitope can be decreased or increased, linear or conformational, detected late or early during infection, in a strain specific manner.     

Molecular mechanics and dynamics of an abasic frameshift in DNA and comparison to NMR data

In a previous publication (Ph. Cuniasse, L.C. Sowers, R. Eritja, B. Kaplan, M.F. Goodman, J.A.H. Cognet, M. Le Bret, W. Guschlbauer and G.V. Fazakerley, Biochemistry 28, 2018 (1989), we determined by two dimensional NMR studies and molecular mechanics calculations the three-dimensional structure of a non-selfcomplementary oligonucleotide: [sequence; see text] where dr, at the center of the first strand, is a model abasic site. In order to explain all the results arising from NMR measurements, we found that an equilibrium between two conformations was necessary. These conformations differ mainly by the sugar pucker of G5 which is C2' endo or C3' endo. The latter is stabilized by addition of counterions between phosphate residues P3 and P4. In this paper, we have constructed systematically, all possible structures as a function of torsion angles delta of dr4 and of G5 by molecular mechanics in the presence or absence of counterions. Since these conformations were not forced with NMR distance measurements, this method allows detailed comparisons between all possible conformations and NMR data. Maps of contour lines of the potential energy, of fits to NMR distance measurements, and of helical twist as a function of torsion angles delta of dr4 and of G5 unravel the difficulties associated with the study of the G5 sugar pucker conformation equilibrium. Sugar puckers and proton distances are very sensitive criteria to monitor molecular dynamics. Relying on these experimental criteria, we have tested many molecular dynamics preparation phases and we propose a new warm-up and equilibration procedure for molecular dynamics. Thus we show with a 290 ps molecular dynamic run that G5 is in conformational equilibrium and that all NMR data are well reproduced.     

Derivatives of antineoplastic antibiotics of the daunorubicin series containing methylurea or nitrosomethylurea residues

Derivatives of antitumour anthracycline antibiotics containing N-methylurea moiety in the carbohydrate ring were obtained by the interaction of methyl isocyanate with daunorubicin, doxorubicin, carminomycin and daunorubicin derivatives, substituted at C-13 or C-14 positions. N-Nitrosation of these compounds yielded modified anthracycline antibiotics containing the N-methyl-N-nitrosourea substituent at C-3' position. Alkaline degradation of these derivatives produced, through corresponding isocyanates cyclic 3'-N,4'-carbonylderivatives. In these anthracycline derivatives with sugar cycles conjugated with oxazoline-2-ones the predominant conformations of sugar ring has changed from 1C4 to 4C1, 2,5B, or B0,3 (shown by 1H NMR spectroscopy). It was demonstrated, both in vitro and in vivo, that introduction of methylurea or cytotoxic methylnitrosourea moieties does not potentiate antimicrobial, cytotoxic or antitumour properties of these compounds.     

Phosphate ester cleavage in ribose-5-phosphate induced by OH radicals in deoxygenated aqueous solution. The effect of Fe(II) and Fe(III) ions.

The reaction of OH radicals and H atoms with ribose-5-phosphate (10(-2) M) in deoxygenated aqueous solution at room temperature (dose-rate 2-1 X 10(17) eV/ml-min, dose 5 X 10(18)-15 X 10(18) eV/ml) leads to the following dephosphorylation products (G-values): ribo-pentodialdose 1 (0-2), 2-hydroxy-4-oxoglutaraldehyde 2 (0-06), 5-deoxy-erythro-pentos-4-ulose 3 (0-1) and 3-oxoglutaraldehyde 4 (0-06). In addition, some minor phosphate free products (total G=0-09) are formed. G(inorganic phosphate) =1-3 and G(H2O2)=0-3. On the addition of 10(-3) M (Fe(III) ions, G (1) and G (3) increase to 0-6 and 0-4 respectively. In the presence of 10(-3) M Fe(II), G(1) and G(3) change to 0-4 and 0-8, respectively. The other dephosphorylation products are suppressed by the iron ions. G(1) also increases on the addition of increasing amounts of H2O2. Each product can be assigned a precursor radical formed by hydrogen abstraction from C-5, C-4 or C-3 of the ribose-5-phosphate molecule. Products 1 and 2 are formed by oxydative dephosphorylation of an alpha-phospho radical with preceeding H2O elimination for product 2. Elimination of H3PO4 from a beta-phospho radical leads to product 3; product 4 is formed by elimination of two molecules of H2O from its precursor radical and hydrolytic cleavage of an enol phosphate bond. Deuterium-labelling experiments and the effects of the iron ions and of H2O2 support the mechanisms proposed. The importance of the dephosphorylation mechanisms for the formation of strand breaks in DNA is discussed with special reference to the effects of the radiosensitizers.     

B3LYP/6-311++G** study of alpha- and beta-D-glucopyranose and 1,5-anhydro-D-glucitol: 4C1 and 1C4 chairs, (3,O)B and B(3,O) boats, and skew-boat conformations

Geometry optimization, at the B3LYP/6-311++G** level of theory, was carried out on 4C1 and 1C4 chairs, (3,O)B and B(3,O) boats, and skew-boat conformations of alpha- and beta-D-glucopyranose. Similar calculations on 1,5-anhydro-D-glucitol allowed examination of the effect of removal of the 1-hydroxy group on the energy preference of the hydroxymethyl rotamers. Stable minimum energy boat conformers of glucose were found, as were stable skew boats, all having energies ranging from approximately 4-15 kcal/mol above the global energy 4C1 chair conformation. The 1C4 chair electronic energies were approximately 5-10 kcal/mol higher than the 4C1 chair, with the 1C4 alpha-anomers being lower in energy than the beta-anomers. Zero-point energy, enthalpy, entropy, and relative Gibbs free energies are reported at the harmonic level of theory. The alpha-anomer 4C1 chair conformations were found to be approximately 1 kcal/mol lower in electronic energy than the beta-anomers. The hydroxymethyl gt conformation was of lowest electronic energy for both the alpha- and beta-anomers. The glucose alpha/beta anomer ratio calculated from the relative free energies is 63/37%. From a numerical Hessian calculation, the tg conformations were found to be approximately 0.4-0.7 kcal/mol higher in relative free energy than the gg or gt conformers. Transition-state barriers to rotation about the C-5-C-6 bond were calculated for each glucose anomer with resulting barriers to rotation of approximately 3.7-5.8 kcal/mol. No energy barrier was found for the path between the alpha-gt and alpha-gg B(3,O) boat forms and the equivalent 4C1 chair conformations. The alpha-tg conformation has an energy minimum in the 1S3 twist form. Other boat and skew-boat forms are described. The beta-anomer boats retained their starting conformations, with the exception of the beta-tg-(3,O)B boat that moved to a skew form upon optimization.     

Lactones 27 [1]: Transformations of γ-lactones fused to a dimethylcyclohexane ring in Absidia cylindrospora cultures

Two saturated (4a,b) and one unsaturated (5) bicyclic γ-lactones containing a dimethylcyclohexane ring were subjected to biotransformation using the fungal strain Absidia cylindrospora. Six new compounds (6–11) and one known (12) [K.W. Rosenmund, H. Herzberg, H. Schutt, Chem. Ber. 87 (1954) 1258] [2] were isolated. All substrates were stereoselectively hydroxylated by the microorganism at either the C-4 (in the case of 4a and 5) or C-2 position (in case of 4a and 4b) giving the corresponding hydroxylactones with tertiary (6 and 9) or secondary (8 and 10) hydroxy groups, respectively.

The hydroxy group was also introduced into C-3 (in the case of 4a) and C-6 (in the case of 4b) positions. The structures of all obtained products were established on the basis of their spectral data. In the case of lactones 8–10 these structures were undoubtedly confirmed by their X-ray analysis.     

Mapping two functional domains of clathrin light chains with monoclonal antibodies

The two forms of clathrin light chains (LCA and LCB) or clathrin-associated proteins (CAP1 and CAP2) have presented an immunochemical paradox. Biochemically similar, both possess two known functional parameters: binding the clathrin heavy chain and mediating the action of an uncoating ATPase. All previously reported anti-CAP mAbs, however, react specifically with only CAP1 (Brodsky, F. M., 1985, J. Cell Biol., 101:2047-2054; Kirchhausen, T., S. C. Harrison, P. Parham, and F. M. Brodsky, 1983, Proc. Natl. Acad. Sci. USA, 80:2481-2485). Four new anti-CAP mAbs are reported here: two, C-7H12 and C-6C1, react with both forms; two others, C-10B2 and C-4E5, react only with the lower form. Sandwich ELISAs indicated that C-10B2, C-4E5, C-6C1, and C-7H12 react with distinct epitopes. Monoclonal antibodies C-10B2 and C-4E5 immunoprecipitate clathrin-coated vesicles (CCVs) and react with CAP2 epitopes accessible to chymotrypsin on the vesicle. These mAbs inhibit phosphorylation of CAP2 by endogenous CCV casein kinase II. In contrast, C-6C1 and C-7H12 react with epitopes that are relatively insensitive to chymotrypsin. CAP peptide fragments containing these epitopes remain bound to reassembled cages or CCVs after digestion. Immunoprecipitation and ELISAs demonstrate that C-7H12 and C-6C1 react with unbound CAPs but not with CAPs bound to triskelions or CCVs. The data indicate that the CAPs consist of at least two discernible structural domains: a nonconserved, accessible domain that is relevant to the phosphorylation of CAP2 and a conserved, inaccessible domain that mediates the binding of CAPs to CCVs.     

Dimeric anthocyanins from strawberry (Fragaria ananassa) consisting of pelargonidin 3-glucoside covalently linked to four flavan-3-ols

Flavanol-anthocyanin complexes were isolated by successive use of Amberlite XAD-7 chromatography, Sephadex LH-20 gel filtration and preparative HPLC from acidified, methanolic extract of strawberries (Fragaria ananassa Dutch.). These purple minor pigments were characterized by UV-Vis spectroscopy, 1D and 2D NMR techniques, and electrospray mass spectrometry to be catechin(4alpha --> 8)pelargonidin 3-O-beta-glucopyranoside (1), epicatechin(4alpha --> 8)pelargonidin 3-O-beta-glucopyranoside (2), afzelechin(4alpha --> 8)pelargonidin 3-O-beta-glucopyranoside (3) and epiafzelechin(4alpha --> 8)pelargonidin 3-O-beta-glucopyranoside (4). The stereochemistry at the 3- and 4-positions of the flavan-3-ol units was based on assumption of R-configuration at C-2. Each of the four pigments occurred in the NMR solvent as a pair of rotamers. Proved by cross-peaks in the 1H-1H NOESY NMR spectra of 1, 2 and 4, the two conformations within each rotameric pair were in equilibrium with each other. Even though 1 and 2 are based on a different aglycone, their structures may be similar to tentatively identified pigments, which have been assumed to contribute to the colour of red wines.     

Structural determinants of blockade of eosinophil activation, adhesion and secretion by synthetic analogs of phomactin

We examined the structural determinants of phomactin analogs to assess their efficacy as antagonist of PAF. Six analogs of phomactin were synthesized to determine their inhibitory effects on adhesion, superoxide release, leukotriene C4 (LTC4) synthesis and [3H]PAF binding in human eosinophils. Phomactin analogs inhibited both PAF- and IL-5-induced eosinophil adhesion. Analog A, which bears an alkene moiety between C-1 and C-14, a ketone at the C-2 position, and an alkyne moiety between C-3 and C-4, had the greatest anti-adhesive effect. Change of the alkene between C-1 and C-14 to an alkane (analog I) decreased the anti-adhesive effect by 2.5-4 fold, while substitution of ketone by hydroxyl (analog G) at the C-2 position caused an 11-fold decrease in the anti-adhesive effect. Substitution of the alkyne moiety between C-3 and C-4 by an alkene (B and E) or alkane (D) blocked completely the anti-adhesive effect. Analogs A and I completely blocked superoxide release from eosinophils caused by phorbol-12-myristate-13-acetate or PAF and LTC4-release caused by fMLP plus cytochalasin B. Change of the alkyne moiety between C-3 and C-4 to an alkene (B and E) or alkane (D) blocked completely these inhibitory effects of phomactin. Analog A decreased the maximal binding of [3H]PAF binding to eosinophils without change of the apparent dissociation constant. We conclude that phomactin analogs are specific non-competitive PAF antagonists and have exceptional efficacy in inhibiting adhesion, metabolic activity and leukotriene secretion in human eosinophils. We further define the structural alterations in the phomactin molecule that regulate its inhibitory functions.     

Human alfa-fetoprotein: isolation and production of monoclonal antibodies.

Alfa-fetoprotein from human cord serum was purified in a single step by hydrophobic interaction chromatography on Phenyl Sepharose CL-4B with a final recovery of alfa-fetoprotein of about 90% and a purification factor of 900. The purified preparation was homogeneous on SDS-PAGE and native PAGE running with a relative molecular weight of 72,000. Monoclonal antibodies against this purified preparation were raised by hybridoma technology using Sp2/0 myeloma cells as a fusion partner. 50% of culture wells exhibited hybrid growth and 7% of these wells contained anti-AFP secreting hybrids. Positive hybrid cells were cloned twice by the limiting dilution method and 8 clones were obtained that secreted monoclonal antibodies. Five of these cell lines (3F6H10, 3F6H4, 3F6H1, 3F6G5 and 3F6G10) were selected at random for purification and characterization purposes. All 5 cell lines secreted monoclonal antibodies of IgG1 subclass which were purified by affinity chromatography on Protein A- Sepharose CL-4B column with a final recovery of 80% and a purification factor of about 13. The purified preparations were homogeneous on SDS-PAGE, native PAGE and IEF. The monoclonal antibodies were highly specific for human alfa-fetoprotein as determined by Western blotting. The affinity constants (K) of these Mab ranged from 10(6) to 10(9) l/mol.     

An ONIOM investigation on anion recognition of alkali–metal complexes with diurea calix[4]arene receptor

The ONIOM(B3LYP/6-31G(d):AM1) optimized structures of complexes of diurea calix[4]arene receptor (L) with alkali metals Li(+), Na(+) and K(+) and their complexes with halide ions F(-), Cl(-), Br(-), oxygen-containing anions HCO(3)(-), HSO(4)(-) and CH(3)COO(-) ions were obtained. Binding energies and thermodynamic properties of complex receptors LiL(+), NaL(+) and KL(+) with these anions were determined. The binding stabilities according to binding energies of LiL(+), NaL(+) and KL(+) associated with anions computed either at the ZPVE-corrected ONIOM(B3LYP/6-31G(d):AM1) or BSSE-corrected B3LYP/6-31 + G(d,p)//ONIOM(B3LYP/6-31G(d):AM1) are in the same order: F(-) > CH(3)COO(-) ≈ HCO(3)(-) > Br(-) ≈ HSO(4)(-) ≈ Cl(-). All the receptors LiL(+), NaL(+) and KL(+) were found to be selective toward fluoride ion.     

ESIMS analysis of fucoidan preparations from Costaria costata, extracted from alga at different life-stages

Four fucoidan fractions from brown alga Costaria costata, collected at different life-stages: vegetative, May (5F2 and 5F3) and generative, July (7F1 and 7F2) collections were characterized. It was found that seaweed synthesizes different set of fucoidans - one with high fucose content and substantial percentage of hexoses and uronic acid and lower sulfate content (7F1, 5F2 and 5F3) and other - highly sulfated galactofucan (7F2). Structural features of fractions 7F2 and 5F3 were predominantly determined by mass spectrometric analysis of low-molecular-weight (LMW) oligosaccharide fragments, obtained by autohydrolysis of 7F2 and mild acid hydrolysis of 5F3 fucoidans. It was found that oligosaccharides from 7F2 fractions were mainly built up of sulfated at C-2 and/or at C-2/C-4 (1→3)-linked α-l-fucopyranose residues. d-Galactose residues, sulfated either at C-2 or C-6, were found as parts of mixed di- and trisaccharides at both termini and, probably, internal. Fucose residues in 5F3 fucoidan fragments were sulfated at C-2 and sometimes at C-4. Galactose residues were sulfated at C-4 and less frequently at C-2. Resistant to hydrolysis fraction was probably a core, built up with fucose, mannose and glucuronic acid. Presumably, oligosaccharide fragments were branches at C-4 of GlcA. They were sulfated at C-2 and sometimes at C-4 (1→3)- and/or (1→4)-linked fucooligosaccharides (sometimes terminated with (1→3)-linked galactose) and sulfated at C-4 or C-2 (1→4)- or, probably, (1→6)-linked galactooligosaccharides, probably, with own branches, formed by (1→2)-linked galactose residues. Unsulfated xylose residues were probably terminal in chains built up of fucose. It was confirmed, that monosaccharide content and structure of fucoidans of vegetative algae changed following its life stage. Generative alga in general produced highly sulfated galactofucan having lower MW along with less sulfated mannoglucuronofucan with higher MW, which was extensively synthesized by vegetative algae.     

Theoretical investigation on the structure and thermodynamic properties of the 2,4-dinitroimidazole complex with methanol

The structure and thermodynamic properties of the 2, 4-dinitroimidazole complex with methanol were investigated using the B3LYP and MP2(full) methods with the 6-31++G(2d,p) and 6-311++G(3df,2p) basis sets. Four types of hydrogen bonds [N–H?O, C–H?O, O–H?O (nitro oxygen) and O–H?π] were found. The hydrogen-bonded complex having the highest binding energy had a N–H?O hydrogen bond. Analyses of natural bond orbital (NBO) and atoms-in-molecules (AIM) revealed the nature of the intermolecular hydrogen-binding interaction. The changes in thermodynamic properties from monomers to complexes with temperatures ranging from 200.0 to 800.0 K were investigated using the statistical thermodynamic method. Hydrogen-bonded complexes of 2,4-dinitroimidazole with methanol are fostered by low temperatures.

Theoretical Investigation on the Binding Specificity of Sialyldisaccharides with Hemagglutinins of Influenza A Virus by Molecular Dynamics Simulations

Recognition of cell-surface sialyldisaccharides by influenza A hemagglutinin (HA) triggers the infection process of influenza. The changes in glycosidic torsional linkage and the receptor conformations may alter the binding specificity of HAs to the sialylglycans. In this study, 10-ns molecular dynamics simulations were carried out to examine the structural and dynamic behavior of the HAs bound with sialyldisaccharides Neu5Acα(2–3)Gal (N23G) and Neu5Acα(2–6)Gal (N26G). The analysis of the glycosidic torsional angles and the pair interaction energy between the receptor and the interacting residues of the binding site reveal that N23G has two binding modes for H1 and H5 and a single binding mode for H3 and H9. For N26G, H1 and H3 has two binding modes, and H5 and H9 has a single binding mode. The direct and water-mediated hydrogen bonding interactions between the receptors and HAs play dominant roles in the structural stabilization of the complexes. It is concluded from pair interaction energy and Molecular Mechanic-Poisson-Boltzmann Surface Area calculations that N26G is a better receptor for H1 when compared with N23G. N23G is a better receptor for H5 when compared with N26G. However, H3 and H9 can recognize N23G and N26G in equal binding specificity due to the marginal energy difference (≈2.5 kcal/mol). The order of binding specificity of N23G is H3 > H5 > H9 > H1 and N26G is H1 > H3 > H5 > H9, respectively. The proposed conformational models will be helpful in designing inhibitors for influenza virus.     

Effects of some alcohols on the conformation of mitochondrial H+-ATPase complex and F1-ATPase from pig heart

The conformations of the H+-ATPase complex and F1-ATPase in low concentrations of methanol, ethanol, n-propanol, iso-propanol and t-butanol were studied by circular dichroism. For F1-ATPase, all but methanol first increased and then decreased the circular dichroism magnitude of helical bands as the alcohol concentration was increased. With ethanol, n-propanol, iso-propanol and t-butanol, the alpha-helix content reached a maximum at about 5% alcohol and began to decrease at 10%. The content of beta-sheet showed the opposite effect, reaching a minimum at 5% and increasing slightly at higher concentrations. None of the alcohols studied had a significant effect on the conformation of the H+-ATPase complex. This difference implies that the alcohols had a greater effect on free F1-ATPase than on the membrane-bound F1-ATPase. The hydrophobic protein F0 and the membrane lipids in the H+-ATPase complex may stabilize and protect F1 from the effects of the alcohols.     

DFT study of alpha- and beta-D-mannopyranose at the B3LYP/6-311++G** level

Thirty-five conformations of alpha- and beta-d-mannopyranose, the C-2 substituted epimer of glucopyranose, were geometry optimized using the density functional (B3LYP), and basis set (6-311++G**). Full geometry optimization was performed on the hydroxymethyl rotamers (gg/gt/tg) and an analytical hessian program was used to calculate the harmonic vibrational frequencies, zero point energy, enthalpy, and entropy. The lowest energy conformation investigated is the beta-tg in the (4)C(1) chair conformation. The in vacuo calculations showed little energetic preference for either the alpha or beta anomer for mannopyranose in the (4)C(1) chair conformation. Results are compared to similar glucopyranose calculations in vacuo where the alpha anomer is approximately 1kcal/mol lower in electronic energy than the beta anomer. In the case of the generally higher energy (1)C(4) chair conformations, one low-energy, low-entropy beta-gg-(1)C(4) chair conformation was identified that is within approximately 1.4kcal/mol of the lowest energy (4)C(1) conformation of mannopyranose. Other (1)C(4) chair conformations in our investigation are approximately 2.9-7.9kcal/mol higher in overall energy. Many of the (3,O)B, B(3,O), (1,4)B, and B(1,4) boat forms passed through transitions without barriers to (1)S(3), (5)S(1), (1)S(5) skew forms with energies between approximately 3.6 and 8.9kcal/mol higher in energy than the lowest energy conformation of mannopyranose. Boat forms were found that remained stable upon gradient optimization. As with glucopyranose, the orientation and interaction of the hydroxy groups make a significant contribution to the conformation/energy relationship in vacuo.