Chemical synthesis of CD52 glycopeptides containing the acid-labile fucosyl linkage

Glycopeptide 1 with the fucosylated trisaccharide, beta-d-GlcNAc(1-->4)[alpha-l-Fuc(1-->6)]-beta-d-GlcNAc, linked to the Asn of CD52 peptide was prepared by two methods, both of which used the free glycosyl Asn 12 and glycotripeptide 21 as key intermediates. Thus, after the trisaccharide was prepared and linked to Asn, the carbohydrate moiety was deprotected to give 12. From 12, 21 was constructed in homogeneous NMP solutions by elongating the peptide chain alone the N-terminus. Though the glycopeptides were easily soluble in NMP, they were barely soluble in diethyl ether, because of the free trisaccharide. Consequently, addition of diethyl ether to the reaction mixtures could precipitate the glycopeptides, and the products were conveniently isolated and purified in the solid form. The coupling of 21 with a free nonapeptide 24 in NMP afforded 1. 1 was also prepared by solid-phase synthesis, using the acid-sensitive 2-chlorotrityl resin. In this case, 21 was attached to the nonapeptide on the resin, and the resulting glycopeptide was then released with dilute acetic acid. Deprotection of the peptide under moderate acidic conditions gave 1. The acid-labile alpha-fucose was not affected in these syntheses.     

Consideration of molecular weight during compound selection in virtual target-based database screening

Virtual database screening allows for millions of chemical compounds to be computationally selected based on structural complimentary to known inhibitors or to a target binding site on a biological macromolecule. Compound selection in virtual database screening when targeting a biological macromolecule is typically based on the interaction energy between the chemical compound and the target macromolecule. In the present study it is shown that this approach is biased toward the selection of high molecular weight compounds due to the contribution of the compound size to the energy score. To account for molecular weight during energy based screening, we propose normalization strategies based on the total number of heavy atoms in the chemical compounds being screened. This approach is computationally efficient and produces molecular weight distributions of selected compounds that can be selected to be (1) lower than that of the original database used in the virtual screening, which may be desirable for selection of leadlike compounds or (2) similar to that of the original database, which may be desirable for the selection of drug-like compounds. By eliminating the bias in target-based database screening toward higher molecular weight compounds it is anticipated that the proposed procedure will enhance the success rate of computer-aided drug design.     

Direct methylation and trifluoroethylation of imidazole and pyridine derivatives

Direct methylation or trifluoroethylation of imidazole and pyridine derivatives using N-methyl bis((perfluoroalkyl)sulfonyl)imides or trifluoroethyl phenyliodonium bis((trifluoromethyl)sulfonyl)imide affords high yields of the corresponding salts. This methodology provides a simple route to a variety of room temperature ionic liquids (RTILs).     

Rapid and high-capacity immobilization of enzymes based on mesoporous silicas with controlled morphologies

Very rapid (< 10 min to reach equilibrium) and high-capacity (up to 533 mg g(-1)) immobilization of enzymes within mesoporous silica has been achieved by finely tuning their morphologies.     

Hemoglobin dendrimers: functional protein clusters

A cluster of cross-linked hemoglobin tetramers was prepared by conjugating active esters to amino groups of a starburst dendrimer. Comparison of oxygen-binding properties of the protein cluster to those of nonclustered species reveals an increase in affinity and a decrease in cooperativity in the cluster. The altered oxygen-binding properties are assigned to protein-protein interactions.     

Convergent synthesis of a GPI containing an acylated inositol

A GPI of sperm CD52 was synthesized by a highly convergent procedure, representing the first chemical synthesis of a complex GPI having an acylated inositol. The presence of a large acyl group resulted in unusual properties and reactions of the relevant intermediates, which gave rise to a number of problems. To overcome the problems and achieve the target molecule, a new synthetic strategy was developed. First, the pseudodisaccharide of 2-O-palmitoylinositol was phospholipidated, and then the trimannose segment and the phosphoethanolamine group were sequentially attached. Global deprotection eventually afforded the sperm CD52 GPI. The method may be useful for the synthesis of other GPIs having an acylated inositol.     

On functorial decompositions of self-smash products

We give a decomposition formula for n-fold self smash of a two-cell suspension X localized at 2. The mod 2 homology of each factor in the decomposition is explicitly given as a module over the Steenrod algebra and in the case where X is formed by suspending one of P²,P²,P² or P², this is a complete decomposition into indecomposable pieces. The method has consequences in the modular representation theory of the symmetric group where it leads to a computation of the submatrix for the decomposition matrix of the group algebra /2[S_n] which correspond to partitions of length 2. In particular this yields a derivation of the explicit formula due to Erdmann which gives the multiplicities in the decomposition of /2[S_n] of the indecomposable projective modules which correspond to those partitions.     

A remark on the finite time singularity of the heat flow for harmonic maps

In this paper we study the finite time singularities for the solution of the heat flow for harmonic maps. We derive a gradient estimate for the solution across a finite time singularity. In particular, we find that the solution is asymptotically radial around the isolated singular point in space at a finite singular time. It would be more desirable to understand whether the solution is continuous in space at a finite singular time.Received: 15 March 2001, Accepted: 16 June 2002, Published online: 17 December 2002     

Monomial bases for -Schur algebras

Using the Beilinson-Lusztig-MacPherson construction of the quantized enveloping algebra of and its associated monomial basis, we investigate -Schur algebras as ``little quantum groups". We give a presentation for and obtain a new basis for the integral -Schur algebra , which consists of certain monomials in the original generators. Finally, when , we interpret the Hecke algebra part of the monomial basis for in terms of Kazhdan-Lusztig basis elements.

     

Multi-Channel FIR HCN Laser Interferometer on HT-7 Tokamak

A Five-channel far-infrared (FIR) hydrogen cyanide (HCN) laser interferometer was developed to measure plasma electron density profile on the HT-7 superconducting tokamak. The structure of the five-channel FIR laser interferometer is described. The laser source used in the interferometer was a continuous wave glow discharge HCN laser with 3.4 m cavity length and 100 mW power output at 337 m wavelength. The temporal resolution was 0.1 ms and the detection sensitivity was 1/12 fringe. Preliminary experimental results measured by the interferometer on HT-7 tokamak are reported.