Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines

In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete formation of the glycan side-chains resulting from a premature sialylation, additional peptide epitopes become accessible to the immune system in mucin-type glycoproteins on tumor cells. These tumor-associated structure alterations constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens, glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor-associated sialyl-T(N), alpha2,6-sialyl-T and alpha2,3-sialyl-T antigens have been synthesized. Employing different linkers such as the allylic HYCRON or the fluoride-sensitive PTMSEL anchor, the antigenic glycopeptide structures were constructed on the solid phase utilizing pre-assembled glycosyl amino acid building blocks prepared in solution by convergent chemical or chemoenzymatic strategies. The proliferation of cytotoxic T cells has been induced applying a construct composed of a sialyl-T(N) MUC1-glycopeptide conjugated with a tetanus toxin T cell peptide epitope.     

Long-time overdamped Langevin dynamics of molecular chains

We present a novel algorithm of constrained, overdamped dynamics to study the long-time properties of peptides, proteins, and related molecules. The constraints are applied to an all-atom model of the molecule by projecting out all components of the nonbonding interactions which tend to alter fixed bond lengths and angles. Because the overdamped dynamical equations are first order in time, the constraints are satisfied by inversion of a banded matrix at each timestep, which is computationally efficient. Thermal effects are included through a Langevin noise term in the equation of motion. Because high-frequency components of the motion have been eliminated, the timestep of the algorithm is determined by the nonbonding forces, which are two to three orders of magnitude weaker than the bonding forces. Using polyalanine as a test example, we demonstrate that trajectories simulating a microsecond of motion can be run about 10³ times faster than an equivalent molecular dynamics simulation. © 1994 by John Wiley & Sons, Inc.     

Silver-catalyzed [2 + 2] cycloadditions of siloxy alkynes

We have described the first [2 + 2] cycloadditions of siloxy alkynes with a range of unsaturated carbonyl compounds. The reactions are efficiently promoted by substoichiometric amount of silver trifluoromethanesulfonimide and display excellent regio- and diastereoselectivity combined with a broad substrate scope. Our studies have established unambiguously the stepwise mechanism of this process and provided evidence for a novel role of silver in the catalytic cycle of the reaction, which involves silver-based complexation and activation of siloxy alkyne toward the subsequent 1,4-addition.     

Sensitized photoconduction in a polydiacetylene crystal (DCHD)

The photoconductivity of DCHD displays a maximum near 3.6 eV coinciding with the maximum of the S_o → S₁ absorption of the carbazole group. It is attributed to a sensitization involving charge transfer from the excited chromophore to the chain. The rate constant for non-radiative decay of the carbazole singlet due to energy transfer to the chain is 1.6 × 10¹³ s^?1, and for charge transfer ≈ 3 × 10¹¹ s^?1.     

Über die Reaktionen von Guanidin bzw. Harnstoff mit Cyanhydrinen

Action of guanidine or urea on cyclohexanone-, cyclopentanone-, cycloheptanone-and acetonecyanohydrine3 a?3 d generates very different products: 3 a reacts with guanidine inDMF to yield 1,3-diazaspiro[4.5]decane-2,4-diimine (5 a). Heating the components without solvent affords 7,14-diazadispiro[5.1.5.2]pentadecan-15-one(7)^15–17, the guanidine not participating in the reaction; similarly3 b is transformed by guanidine to a pentacyclic dispirocompound (possible formulae19 and20), whereas3 d reacts to give 3,3,5,5-tetramethylpiperazine-2,6-dione(21)¹⁹. In 3-pentanone guanidine-cyanide condensates itself to give 2,4-diamino-triazine (22)^{21, 22}. Action of urea on3 a?3 d yields the 4-imino-1,3-diazaspiroalkan-2-ones6 a?6 c and the 4-imino-5,5-dimethylimidazolidin-2-one6 d ^6–8 resp. If the reaction of urea and3 d is carried out inDMF, however, 5,5-dimethyl-4-ureido-3-imidazolin-2-one (28) (or the tautomeric carbamoyliminoimidazolidinone27) is produced. The structures of the compounds prepared are proved by NMR-, IR- and mass spectra.     

Redox site confinement in highly unsymmetric dimanganese complexes

A set of highly preorganized pyrazolate-bridged dimanganese complexes L(Mn)MnX have been prepared and structurally characterized. They can be described as hybrid organometallic/Werner-type systems that consist of a low-spin CpMn(I)(CO)2 subunit (Mn1) and a proximate tripodal tetradentate {N4} binding pocket accommodating a high-spin Mn(II) ion (Mn2), with Mn...Mn distances of approximately 4.3 A and different coligands bound to Mn2. Density functional theory (DFT) calculations (both the hybrid B3LYP and the pure BP86 functionals and the all-electron basis sets 6-311G and 6-311G*) confirm that the valence alpha and beta Kohn-Sham molecular orbitals (MOs) of these mixed-valent Mn(I)Mn(II) compounds have predominant Mn(3d) character and an almost perfectly localized nature: all five unpaired electrons are essentially localized at the Werner-type Mn2, whereas Mn1 possesses an effective closed-shell structure with the MOs of highest energy centered there. One-electron oxidation occurs in a clean process at approximately E(1/2) = -0.6 V (versus ferrocene/ferrocinium), giving the low-spin/high-spin Mn(II)Mn(II) species. UV/vis and IR spectroelectrochemistry as well as a detailed theoretical analysis reveal that the redox process takes place with strict site control at the organometallic subunit, while it does not significantly influence the spin and charge distribution on the Werner-type site. Positions and shifts of the nu(C[triple bond]O) absorptions are largely reproduced by the DFT calculations. These systems thus represent an exceptional example of the effect the unsymmetry of a dinucleating ligand scaffold has on the spin and charge distribution in homobimetallic complexes and might offer interesting prospects for the study of the cooperative effects of bimetallic arrays.     

Recent advances in the synthesis of well-defined glycopolymers

Glycopolymers are receiving increasing interest due to their application in areas, such as glycomics, medicine, biotechnology, sensors, and separation science. Consequently, new methods for their synthesis are constantly being developed, with an increasing emphasis on the preparation of well-defined polymers and on the production of complex macromolecular architectures such as stars. This review covers recent developments in the synthesis of glycopolymers, with a particular emphasis on (i) the use of controlled radical polymerization to prepare well-defined glycopolymers from unprotected monomers and (ii) postpolymerization modification strategies using reactive polymer precursors (including “click” reactions). Recent work on the production of glycosylated polypeptides, which are under investigation as mimics of naturally occurring glycoproteins, is also included. The authors offer some suggestions as to future developments and remaining challenges in this topical area of polymer chemistry. © 2007 Wiley Periodicals, Inc. J Polym Sci PartA: Polym Chem45: 2059–2072, 2007     

Structure Determination of a Complex Tubular Uranyl Phenylphosphonate, (UO(2))(3)(HO(3)PC(6)H(5))(2)(O(3)PC(6)H(5))(2).H(2)O, from Conventional X-ray Powder Diffraction Data

The three-dimensional structure of a complex tubular uranyl phosphonate, (UO(2))(3)(HO(3)PC(6)H(5))(2)(O(3)PC(6)H(5))(2).H(2)O, was determined ab initio from laboratory X-ray powder diffraction data and refined by the Rietveld method. The crystals belong to the space group P2(1)2(1)2(1), with a = 17.1966(2) ?, b = 7.2125(2) ?, c = 27.8282(4) ?, and Z = 4. The structure consists of three independent uranium atoms, among which two are seven-coordinated and the third is eight-coordinated. These metal atoms are connected by four different phosphonate groups to form a one-dimensional channel structure along the b axis. The phenyl groups are arranged on the outer periphery of the channels, and their stacking forces keep the channels intact in the lattice. The determination of this structure which contains 50 non-hydrogen atoms in the asymmetric unit, from conventional X-ray powder data, represents significant progress in the application of powder techniques to structure solution of complex inorganic compounds, including organometallic compounds.