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Hexabutoxytriphenylene is used for the synthesis of hexabutoxytribenzo[a,g,m]coronenes. The analysis has shown that these molecules can adopt a 'double concave' conformation, thus making them ideal hosts for the binding of different guest molecules at each face.

The rotational microwave spectroscopy was used to identify and characterize two conformers of 3-heptyne, the C [triple bond] C elongated analogue of pentane and ethyl propyl acetylene. The results reveal that the most stable conformer of pentane has anti-anti (AA) conformations about the central C-C bonds (C.sub.2v) and the next most stable has a gauche dihedral angle (GA, [C.sub.1]).

Laser-induced fluorescence (LIF) spectroscopy and fluorescence-detected ultraviolet (UV)-UV and infrared (IR)-UV double-resonance spectroscopy are used to study the structure of jet-cooled L-tyrosine (L-Tyr). The comparison of the results of L-Tyr and L-phenylalanine have shown that conformers of L-Tyr existing under jet-cooled condition have side-chain conformers similar to conformers B, D, E, and X of L-phenylalanine.

The decay of fluorescence lifetime can be correlated to the structure of the macromolecule to which the fluorophore is attached. The autocorrelation function of delay time between the excitation and emission of a single photon is proportional to the autocorrealtion function of the square of the fluorescence lifetime.

The conformational behavior of typtophan (Trp) was investigated for the compound isolated in low-temperature argon and xenon matrixes by infrared spectroscopy and DFT(B3LYP)/6-311++G(d,p) calculations. Theoretical analysis revealed two important factors in stabilizing the structures of the Trp conformers, the H-bond type and electrostatic interactions.

The vibrational spectroscopy, gas electron diffraction (GED), and quantum chemical calculations were used to study the molecular structure and conformational properties of N-pentafluorosulfur(sulfuroxide difluoride imide), S[F.sub.5]N=S(O)[F.sub.2]. The results have concluded that the syn form in which the N-S bond staggers the two S-F bonds of the S(O)[F.sub.2] group is sterically favored with respect to the anti conformer in which the N-S bond staggers the S=O bond and one S-F bond.

Quantum mechanical calculations are used to investigate the intrinsic conformational preferences of [alpha],[alpha]-diphenylglycine, a simple [alpha],[alpha]-dialkylated amino acid bearing two phenyl substituents on the [alpha]-carbon, in both the gas phase and aqueous solution. A set of force-field parameters are developed for classical Molecular Mechanics and Molecular Dynamics simulations are carried out in aqueous solutions to validate these parameters.

The systematic large-scale theoretical investigations of the glycosaminoglycan building units are reported. The computations that include the effect of solvation has indicated that in water the relative stability of [Na.sup.+]...ligand ionic bonds is diminished and the computed interaction energy in water is small and negative.

A comparative study of the conformational ensembles and free energies of solvent polarization from explicit, as well as an implicit solvation is used to analyze the secondary structure bias in the generalized born (GB) solvent models. Despite the fact that GB models can be implemented only by optimizing the effective Born radius calculations, analysis has proved to be extremely beneficial, as the GB function proves the agreement between the self and interaction energies.

Alpha-sarcin is an exquisitely specific ribonuclease that binds and cleaves a single phosphodiester bond in the large rRNA of the eukaryotic ribosome, inactivating it and to better understand this activity, the contributions of the active site residues to the conformational stability is determined as a function of pH using variant proteins containing uncharged substitutes. A comparison of the stability vs. pH profiles determined by thermal denaturation experiments reveals that charged forms of Glu 96 and His 137 compromise the enzyme's stability, lowering it.

Conformational analyses of 3'-[1E-2-(4-R-phenyl)ethenyl]-2,2':5',2' -terthiophenes revealed three important dihedral angles, and the potential energy surfaces for each of these angles calculated for three R-pet molecules using the HF/3-21G(d) method is discussed. It is therefore concluded that the experimental electronic absorption spectra qualitatively support the positions and trends in energies of the R-pet molecular orbital.

Caenhorhabditis elegans Uncl04 kinesin transports synaptic vesicles at rapid velocities. Unc104 is primarily monomeric in solution, but recent motility studies suggest that it may dimerize when concentrated on membranes. Using cryo-electron microscopy, we observe two conformations of microtubule-bound Unc104: a monomeric state in which the two neck helices form an intramolecular, parallel coiled coil; and a dimeric state in which the neck helices form an intermolecular coiled coil. The intramolecular folded conformation is abolished by deletion of a flexible hinge separating the neck helices, indicating that it acts as a spacer to accommodate the parallel coiled-coil configuration. The neck hinge deletion mutation does not alter motor velocity in vitro but produces a severe uncoordinated phenotype in transgenic C. elegans, suggesting that the folded conformation plays an important role in motor regulation. We suggest that the Unc104 neck regulates motility by switching from a self-folded, repressed state to a dimerized conformation that can support fast processive movement.

A thermally induced irreversible conformational transition of amylose tris(3,5-dimethylphenylcarbamate) (i.e., Chiralpak AD) chiral stationary phase (CSP) in the enantioseparation of dihydropyrimidinone (DHP) acid racemate was studied for the first time by quasi-equilibrated liquid chromatography with cyclic van't Hoff and step temperature programs and solid-state ([sup.13]C CPMAS and [sup.19]F MAS) NMR using ethanol and trifluoroacetic acid (TFA)-modified n-hexane as the mobile phase. The conformational transition was controlled by a single kinetically driven process, as evidenced by the chromatographic studies. Solid-state NMR was used to study the effect of the temperature on the conformational change of the solvated phase (with or without the DHP acid enantiomers and TFA) and provided some viable structural information about the CSP and the enantiomers.

A methodology for conformational analyses of polymers having long side chains was presented. By incorporating the solvents into the MD simulations, a process reproduction of the experiment is possible.

The polarizable continuum method at the B3LYP/6-31G level is used to calculate the Z/E isomer ratios for codeinone-6-oxime and 7,8-dihydro-codeinone-6-oxime in chloroform and in a water:acetonitrile 85:15 (volume ratio) mixture. B3LYP/6-31G optimized geometric parameters are almost constant for formaldoxime, the C-ring model compound, (methoxy-methyl)vinyl-ketone oxime, and codeinone oximes in the absence of special structural features.

The use of the PBE0 hybrid density functional theory method in conjunction with the COSMO solvation model allowed us to reproduce, both qualitatively and quantitatively, the experimentally observed conformational compositions of 2-substituted and 2,7-disubstituted methylenecyclohexanes. An analysis revealed several different interactions that influence the overall equilibrium. It was found that the endo (general) anomeric effect plays a significant role in the equilibrium and that the "unsaturation effect" possibly comprises two effects. Key words: conformational analysis, methylenecyclohexanes, anomeric effect, unsaturation effect.

The conformations of a series of derivatives of the disaccharide [alpha]-L-fucopyranosyl-(1 [right arrow] 3)-2-acetamido-2-deoxy-D-glucopyranoside, part of the [Le.sup.x] determinant, were studied by molecular modelling using the MM[3.sup.*] forcefield and by [sup.1]H NMR spectroscopy. Unusually shielded O-benzyl protons were observed in the [sup.1]H NMR spectrum of phenyl 2,3,4-tri-O-benzyl-[alpha]-L-fucopyranosyl-(1 [right arrow] 3)-2-deoxy-2-phthalimido-1-thio-[alpha]-D-glucopyranoside and assigned to the 2-O-benzyl group. This observation was explained by a shift in the population of the conformational mixture present about the glycosidic linkage from the positive [PSI] region in the unsubstituted disaccharide to the negative [PSI] region induced by [pi]-stacking between the phthalimide and the 2-O-benzyl phenyl ring. The experimental nuclear Overhauser enhancements confirm the accuracy of the calculations. Key words: disaccharide, conformation, [pi]-stacking, [Le.sup.x] determinant, NOE measurements, MM3 calculations.

Byline: J. Mazur (1), R. L. Jernigan (3,4), A. Sarai (5) Keywords: propeller twist; DNA flexibility; stress--strain relation Abstract: DNA is an extensible molecule, and an extended conformation of DNA is involved in some biological processes. We have examined the effect of elongation stress on the conformational properties of DNA base pairs by conformational analysis. The calculations show that stretching does significantly affect the conformational properties and flexibilities of base pairs. In particular, we have found that the propeller twist in base pairs reverses its sign upon stretching. The energy profile analysis indicates that electrostatic interactions make a major contribution to the stabilization of the positive-propeller-twist configuration in stretched DNA. This stretching also results in a monotonic decrease in the helical twist angle, tending to unwind the double helix. Fluctuations in most variables initially increase upon stretching, because of unstacking of base pairs, but then the fluctuations decrease as DNA is stretched further, owing to the formation of specific interactions between base pairs induced by the positive propeller twist. Thus, the stretching of DNA has particularly significant effects upon DNA flexibility. These changes in both the conformation and flexibility of base pairs probably have a role in functional interactions with proteins. Author Affiliation: (1) Advanced Biomedical Computing Center, SAIC, NCI-FCRDC, Frederick, MD, 21701, USA (2) 104 Brooksby Village Dr., Peabody, MA, 01960, USA (3) Laboratory of Experimental and Computational Biology, NCI, NIH, Bethesda, MD, 20892-5677, USA (4) Laurence H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, IA, 50011-3020, USA (5) RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan Article History: Registration Date: 12/10/2004

Time-resolved NMR spectroscopy is used to study changes in protein conformation based on the elapsed time after a change in the solvent composition of a protein solution. The use of a micromixer and a continuous-flow method is described where the contents of two capillary flows are mixed rapidly, and then the NMR spectra of the combined flow are recorded at precise time points. The distance after mixing the two fluids and flow rates define the solvent--protein interaction time; this method allows the measurement of NMR spectra at precise mixing time points independent of spectral acquisition time. Integration of a micromixer and a microcoil NMR probe enables low-microliter volumes to be used without losing significant sensitivity in the NMR measurement. Ubiquitin, the model compound, changes its conformation from native to A-state at low pH and in 40% or higher methanol/water solvents. Proton NMR resonances of the His-68 and the Tyr-59 of ubiquitin are used to probe the conformational changes. Mixing ubiquitin and methanol solutions under low pH at microliter per minute flow rates yields both native and A-states. As the flow rate decreases, yielding longer reaction times, the population of the A-state increases. The micromixer-NMR system can probe reaction kinetics on a time scale of seconds.

The influence exerted on an integral membrane protein by its environment using the light-harvesting complex (LHI) of purple bacteria as a model, is studied. It is concluded that membrane environment significantly narrows the statistical distribution of conformational states available to the LH1 complex in comparison to the corresponding state distribution observed for the same detergent-solubilized protein.

A computational study of 5-substituted cyclopentadienes is presented. The substituents considered are the group 14-17 elements of the second through fifth periods, saturated by hydrogens as needed to fulfill normal valence requirements. The conformational characteristics are examined and rationalized using bond-antibond interactions and steric arguments. Trends in vibrational frequencies are discussed and compared with experiment where possible. Key words: cyclopentadiene, ab initio, spectra.

Research has been conducted on reduced recombinant human macrophage colony stimulating factor beta. The folding events of this factor investigated via monitoring folding kinetics by exclusion chromatography are discussed.

Research has been conducted on tricyclic pyridones with a fused seven-membered ring. The synthesis of these compounds is described, and the results demonstrate that they exhibit atropisomerism and exist in enantiomeric forms.

Research has been conducted on diamagnetic and paramagnetic lanthanide chelates. The NMR study of the chelates' solution structure and the analysis of Gd (super)3+ complexes' relaxation properties are reported.

Research has been conducted on polymethylated macrocyclic ligands. The synthesis of these ligands has been carried out and their conformational properties have been investigated via the use of nuclear magnetic resonance.

Research has been conducted on [1,3,4]-oxadiazinan-2-ones. The conformational properties of this compound have been investigated via the use of X-ray crystallography and variable temperature (super)13 C NMR spectroscopy and the results are reported.

Research has been conducted on conformations of wild-type ribonuclease A. The study of these conformations carried out under folding conditions via the use of steady-state and time-resolved fluorescence energy-transfer measurements and via the analysis of intramolecular distance distributions in several mutants is presented.

Research has been conducted on calcium-binding protein calmodulin, important for eukaryotic signal transduction. Results demonstrate the existence of Ca (super)2+ -dependent communication between the domains indicating that spatially distant residues can respond to Ca (super)2+ binding in calmodulin's N-domain.

Research has been conducted on the photoactive yellow protein. The protein's light-induced structural change has been investigated via the use of small-angle X-ray scattering and its light-induced conformation change is discussed.

Research has been conducted on the aminophosphonic acids and their derivatives. The use of the tert-butylphosphonoacetate moieties in producing mono- and bicyclic alpha-Boc-aminophosphonate systems is described.

Research has been conducted on spiropentyl acetate and spiropentylcarboxylic acid methyl ester, the chiral monosubstituted derivatives of spiropentane. The synthesis of these compounds in optically active form has been carried out and the results of their conformational and configurational analysis performed via the use of vibrational dichroism and infrared spectroscopies are discussed.

Research has been conducted on the bianthrone X-ray crystallographic structures. The use of density functional theory calculations in investigating these structures is described and the presence of central C-C bonds and gauche conformation has been confirmed.

The chiral bis(phosphine) ligand P,P'-1,2-phenylenebis[(1R,2S,4R,5S)-2,5-dimethyl-7-phosphabicyclo[2.2.1] heptane], [(R,S,R,S)-Me-PennPhos] (1) reacts with trans-Ru[Cl.sub.2)(NBD) [Py.sub.2] (NBD = norbornadiene, Py = pyridine) (2) in C[H.sub.2][Cl.sub.2] at 45[degrees]C to form two diastereomers of the triply chloride bridged cation [[{(1)Ru[Py}.sub.2]([micro]-[Cl).sub.3])][Cl.sup.-]] (3) in the ratio 1:3. The isomers were studied by NMR spectroscopy and separated by crystallization from [CD.sub.2][Cl.sub.2]-hexanes mixture. The major diastereomer is one of the anti-diastereomers and contains face-sharing bioctahedral diruthenium (Ru(II, II)) molecules with a Ru--Ru distance of 3.289 [Angstrom]. This diastereomer crystallizes in the monoclinic space group C2 (No. 5) with the cell dimensions a([Angstrom]) = 28.102(2), b([Angstrom]) = 20.5344(15), c([Angstrom]) = 12.7692(10), [beta]([degrees]) = 95.7411(16), V([[Angstrom].sup.3]) = 7331.6(9), and Z = 4. The Me-PennPhos ligand adopts an unexpected bent, non-C2 symmetric conformation upon coordination to ruthenium. Key words: PennPhos crystal structure, diruthenium complexes, triply bridged complexes, bisphosphine ruthenium complexes.

Research has been conducted on the persubstituted cyclopentadiene and -dienyl moieties. The threshold rotational pathways and conformational preferences of these moieties have been investigated via the use of structure correlation principles and the details are reported.

Research has been conducted on the 5.6-spirolactams. The conformational preference of these compounds has been investigated via the prepared Ac-{Gly-Leu}-Met-NH (sub)2 derivatives (S,S,S) and (S,R,S) with the tripeptidic C-terminal region present in tachykinins.

Research has been conducted on the dipeptide isosteres produced by L-leucine and meso-tartaric acid derivatives. The isosteres have been inserted into a small peptide and the conformational features of the resulting peptides have been studied via IR, NMR and molecular modeling methods revealing the presence of the reverse turn conformation in all the structures.

The equilibrium geometries of the isoelectronic Z[Ph.sup.0, [+ or -] 1.sub.4] (Z = B, C, N) molecules have been optimized, in [S.sub.4] and [D.sub.2d] symmetries, at the HF/6-31G(d,p) and B3LYP/6-31G(d,p) levels, with the phenyl rings constrained to be planar. The ground-state conformations of all three species are shown to be of [S.sub.4] symmetry, but the difference of the energies of the [S.sub.4] and the [D.sub.2d] conformations is estimated to amount to only ~1 kcal [mol.sup.-1], with a barrier to concerted rotational reorientation of the phenyl rings of ~5.0 kcal [mol.sup.-1] for B[Ph.sup.1.sub.4], ~6.4 kcal [mol.sup.-1] for C[Ph.sub.4], and ~7.9 kcal [mol.sup.-1] for N[Ph.sup.+.sub.4]. A redetermination of the crystal structure of C[Ph.sub.4] from -60[degrees]C X-ray data agrees with the results of previous determinations at ambient temperature; the C[Ph.sub.4] molecule in the crystal is slightly compressed along the [S.sub.4] axis relative to the free molecule, otherwise the geometries of the two are essentially the same. Correlations between the optimized geometric parameters of the Z[Ph.sup.0, [+ or -] 1.sub.4] molecules have been examined and analyzed in detail, as have the substitution-induced changes in the geometry of the phenyl ring. The results confirm and strengthen the conclusions from the statistical studies by Domenicano et al. on the geometry of benzene rings monosubstituted by atoms of elements from the first row of the Periodic system. Key words: tetraphenylborate, tetraphenylmethane, tetraphenylammonium, ab initio molecular geometries.

Some imidazolidine-2,4-dione (hydantoin) and thiazolidine-2,4-dione (TZD) derivatives with a 1H-pyrrol-2-ylmethylene substituent at the 5-position (1-8) have been synthesized via an aldol condensation reaction. A mixture of Z- and E- stereoisomers was obtained, as confirmed by HPLC and NMR studies. Assignment of the stereochemistry was achieved through chemical shift knowledge, NOE, and [sup.3][J.sub.H,C] data. The conformation of the molecules depends on the configuration at the double bond. While the (NH,C cis) form is the most stable conformer for the E-isomer, the (NH,C trans) form is the preferred conformer for the Z-isomer. The temperature coefficients of the NH pyrrole protons reveal the existence of an intramolecular hydrogen bond for the E-isomers. Key words: hydantoin, TZD, NMR spectroscopy, conformational analysis, temperature coefficient.

Research has been conducted on the unsaturated thiacrown ethers. The reactions of these ethers with CF (sub)3 COOAg in acetone have produced silver(I) complexes and the crystal structure of one of the complexes indicate that the geometry around the silver atom is coplanar.

Research has been conducted on the tellurium(II) dithiolates. The preparation of these thiolates carried out via the new developed methods is described.

Research has been conducted on the amino alcohol- and diamino-cis-decalins. The synthesis of these compounds and their conformational properties have been investigated and the results indicate that the equilibrium ratio depends on the decalin ring system substituents and the solvent.

Research has been conducted on the L-glutamic acid analogues. The synthesis and stereochemical characterization of 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acid isomers have been carried out and the details are reported.

Research has been conducted on the conformational archetypal families. The cyclononanes from these families have been transformed into the stochastically generated cis-cyclononenes via conversion of the single bond synclinal endocyclic torsion angles and geometry optimization and the details are reported.

Biased stochastic conformational searches using the MMFF94 force field and the Born continuum solvation model were applied to the molecular modeling of the Lewis X ([Le.sup.x]) trisaccharide ([beta-D-Gal-(1,4)-[[alpha]-L-Fuc-(1,3)]-[beta]-DGlcNAc-OH) and three [Le.sup.x] analogues, in which each of the three sugar units was replaced by another sugar residue, i.e., N-acetyl-glucosamine by glucose, galactose by glucose, and fucose by rhamnose. The stochastic search accurately identified a lowest energy conformation of the [Le.sup.x] determinant that corresponds to the reported conformations of [Le.sup.x] deduced experimentally in the solid state by X-ray crystallography and in solution by NMR measurements. In this conformation stacking exists between the galactosyl and fucosyl residues. Five new local minima for the [Le.sup.x] trisaccharide were found within 3 kcal [mol.sup.-1] of the global minimum using the stochastic search and metric scaling. Modeling studies of the analogues showed that the stacking observed in the [Le.sup.x] trisaccharide was maintained when either galactosyl or N-acetylglucosamine were replaced by glucosyl residues. In contrast, substitution of the fucose residue by rhamnose led to two conformers in which stacking of the galactose and rhamnose residues was no longer maintained. These results indicate that the substitution of the non-reducing end galactosyl or N-acetyl-glucosaminyl residues by a glucose unit in the dimeric Lewis X ([dimLe.sup.x]) tumour associated antigen could help in the development of a vaccine that crossreacts with [dimLe.sup.x] but no longer displays [Le.sup.x] associated three-dimensional epitopes also presented by non-cancerous cells. In contrast, an analogue in which the fucosyl residue is replaced by rhamnose does not constitute a good vaccine candidate, since our results indicate that this substitution will induce an important conformational change that is likely to abolish cross-reactivity with the natural [dimLe.sup.x] tumor associated antigen. Key words: molecular modeling, stochastic, conformational analysis, Lewis X, oligosaccharide.

The capsular polysaccharide of E. coli K92 (K92P) contains elements in common with the capsular polysaccharides of both groups B and C N. meningitidis, and may therefore form the basis of a bivalent vaccine. In an attempt to augment the cross-protective immune response to group B meningococci, the N-acetyl groups of the K92P were replaced by N-propionyl groups (NPrK92P) and conjugated to protein. This strategy had previously been applied with success to the poorly immunogenic capsular polysaccharide of group B meningococcus (GBMP), and the bactericidal epitope was found to be exclusively mimicked by extended helical segments of the NPrGBMP. The NPrK92P-conjugate, in relation to a K92P-conjugate, failed to enhance the response to GBMP but did generate a measurable response to NPrGBMP, but only at the expense of a greatly reduced GCMP response. Despite the presence of an immune response to NPrGBMP, the anti-NPrK92 serum was not bactericidal. Competitive inhibition studies with NPrGBMP oligosaccharides suggested the NPrK92 antibodies could not cross-react with the protective epitope on group B meningococci, as defined by extended helical segments of the NPrGBMP, but only recognized short non-bactericidal NPrGBMP epitopes. This hypothesis was supported from the conformational and molecular dynamics studies of the K92P, which demonstrated a lack of extended conformations that resemble the GBMP extended epitope. Indeed, the conformational properties of the K92P more closely resembled those of the GCMP, thereby explaining the observed moderate cross-protection of the K92P antiserum towards group C meningococci. Thus, on the basis of these results, it can be concluded that K92P, regardless of N-propionyl modification, will not serve as an effective single vaccine component against both groups B and C meningococci. Key words: conjugate vaccine, Neisseria meningitidis, polysialic acid, NMR, molecular dynamics.

The enzyme [beta](1[right arrow]4)-glucosyltransferase (BGT) catalyses the transfer of glucose from uridine diphosphoglucose (UDP-Glc) to 5-hydroxymethylcytosine (5-HMC) bases in double-stranded DNA. Potential inhibitors of BGT were developed by structure-based design and synthesized. The designed inhibitors 1-6 provide conformational mimicry of the transition state in glucosyltransfer reactions. The key synthetic steps involve a Michaelis-Arbuzov reaction followed by coupling with uridine-5'-morpholidophosphate as activated UMP derivative. The compounds were tested for in vitro inhibitory activity against BGT and the inhibition kinetics were examined. Three of the designed molecules were found to be potential inhibitors of BGT having I[C.sub.50] values in the micromolar ([micro]M) range. Useful structure-activity relationships were established which provide guidelines for the design of future generations of inhibitors of BGT. Key words: [beta]-glucosyltransferase, transition state, enzyme inhibitors, structure-based design, synthesis.

Previous studies from our laboratory have indicated that the lipopolysaccharide (LPS) from Mannheimia haemolytica serotype A1 contains both L-glycero-D-manno-heptose and D-glycero-D-manno-heptose residues. NMR methods making use of 1D [sup.1]H selective excitation and 2D ([sup.1]H, [sup.13]C) and ([sup.1]H, [sup.31]P) heteronuclear experiments were used for the structural determination of the major core oligosaccharide components of the deacylated low-molecular-mass LPS obtained following sequential treatment with anhydrous hydrazine and aq KOH. The core oligosaccharide region was found to be composed of a branched octasaccharide linked to the deacylated lipid A moiety via a 3-deoxy-4-phospho-o-manno-oct-2-ulosonate residue having the structure, [alpha]-D-Glc-p-(1 [down arrow] 6 [beta]-D-Galp-(1-7)-D-[alpha]-D-Hepp-(1-6)-D-[alpha]-D-Hepp-(1-6) -[beta]-D-Glcp-(1-4)-L-[alpha]-D-Hepp-(1[right arrow] 3 [up arrow] L-[alpha]-D-Hepp-(1-2)-L-[alpha]-D-Hepp-(l Heterogeneity was found to be present at several linkages. NMR methods were devised to distinguish between the diastereomeric forms of the heptose residues. Synthesized monosaccharides of L-D- and D-D-heptose were used as model compounds for analysis of the [sup.1]H and [sup.13]C NMR chemical shifts and proton coupling constants. Molecular modeling using a Monte Carlo method for conformational analysis of saccharides was used to determine the conformation of the inner core of the oligosaccharide and to establish the stereochemical relationships between the heptoses. Key words: LPS, NMR, conformation, oligosaccharide, heptose.

Heparin-like hexasaccharide 3 and octasaccharide 4 have been synthesized using a convergent block strategy and their solution conformations have been determined by NMR spectroscopy. Both oligosaccharides contain the basic structural motif of the regular region of heparin but have been constructed as to display negatively charged sulfate groups only on one side of their solution helical structures. This charge distribution along the saccharide chain has been designed to get insight into the proposed mechanism for fibroblast growth factors (FGFs) activation that involves heparin-induced FGF dimerization. Key words: heparin oligosaccharides, synthesis design, conformational analysis, FGF activation.

Transannular Diels-Alder (TADA) adducts constitute a collection of rigid structures, whose conformational diversity is rich. It is possible to design such specifically functionalized molecules capable of binding to known biological targets by molecular modelling MCSS-HOOK (multiple copy simultaneous search). Here we show that such carefully designed compounds can be easily built from small synthons. TADA adducts are very interesting due to their huge conformational diversity, their rigidity (biological interest), and their ease of synthesis (chemical interest). Key words: tricycles, synthesis, transannular Diels-Alder, macrocyclization, conformation, diversity.