J. Fraser Stoddart

Bio: J. Fraser Stoddart is an academic researcher from Northwestern University. The author has contributed to research in topics: Catenane & Supramolecular chemistry. The author has an hindex of 147, co-authored 1239 publications receiving 96083 citations. Previous affiliations of J. Fraser Stoddart include Zhejiang University & Northwest University (United States).

The extramolecular chemical approach to enzyme analogues

Abstract: result and others obtained with the various analogues suggest that, while enzyme-substrate hydrogen bonding may play a role in the A-kinase catalysed phosphoryl group transfer reactions, the a-N-methylated and depsi-containing peptide 1 analogues react at relative rates which require additional explanations. Among the explanations for our results that must be considered are the possibilities that the substitutions of N-methyl groups in the amide bonds cause disruptive peptide-enzyme steric interactions or that intrapeptide steric interactions could prevent a particular peptide analogue from assuming the conformation recognizable by A-kinase. The nature of such steric interactions has been probed in the second aspect of our work (Bramson et al., 1987) which is briefly described herein. As already mentioned, by means of studies utilizing n.m.r. spectroscopy evidence has been obtained that A-kinase probably binds Leu-Arg-Arg-Ala-Ser-Leu-Gly, peptide 1, in one of two extended coil conformations (A or B, described by Rosevear et al., 1984). We have considered, therefore, the possibility that the relative reactivities of a series of N-methylated peptides based on the structure of peptide 1 might be related to the ease with which each peptide can assume the A or B Conformation. The N-methylated peptides which we examined are those illustrated in Table 1 and also the additional ones illustrated in Table 2. Utilizing computer graphics, on the basis of estimates of the magnitude of the steric interactions that would be induced by N-methylation of the amide groups in peptide 1 derivatives locked in either conformation, the ability of each peptide analogue to form a particular conformation was predicted. We found that there was a good correlation between the catalytic activity of A-kinase in the phosphorylation of the N-methylated peptides and the ability of each peptide to form conformation A but not B. To test these findings further we probed the possibility that the reactivity of a relatively unreactive N-methylated peptide might be partially restored by a second change which allowed the peptide to assume conformation A. The finding that such restoration could be achieved together with our other results suggests that when peptide 1 is bound in the enzymic active site it has a conformation which resembles structure A much more closely than structure B (Bramson et al., 1987). In the third aspect of our work we have probed whether when other protein kinases are observed to catalyse the phosphorylation of the same peptide sequences as does A-kinase, the protein kinases utilize the same conformation of the peptide in their reactions (Thomas et al., 19873). We have employed, therefore, the reactions of the conformationally restricted N-methylated peptides which have been utilized as substrates for A-kinase in examining the conformational requirements of the cyclic GMP-dependent protein kinase (G-kinase). The G-kinase is homologous in sequence to A-kinase (Taiko et al., 1984) and has comparable substrate specificities (Lincoln & Corbin, 1977). Our kinetic results with the N-methylated peptides show that, despite the ability of the G-kinase to bind the peptides in a conformation resembling that of conformation A, the Genzyme is more tolerant of backbone methylation than in A-kinase. As a result, while the reactivity of the G-kinase with the prototypic peptide substrate Leu-Arg-Arg-Ala-SerLeu-Gly, peptide 1, is about 10-fold less than the reactivity with the A-kinase, as assessed from the relative magnitudes of k,,,/K,, when the parent peptide was N-methylated at the amide group of the Ser’ residue, the resultant peptide substrate was at least 700-fold more reactive with G-kinase than with A-kinase. Our observations with the peptide which is N-methylated at the phosphorylatable serine residue of peptide 1 show that backbone methylation can represent an approach to making peptide substrates which are selective for a particular kinase (Thomas et al., 19873). This finding encourages us to pursue the possibility that N-methylation of peptides might provide a method for targeting peptidebased inhibitors to selected protein kinases. Partial support of this research by National Institutes of Health Grant GM 32204 is gratefully acknowledged.

Viologen Tweezers to Probe the Force of Individual Donor-Acceptor π-Interactions.

Abstract: Donor–acceptor (DA) π-interactions are weak attractive forces that are exploited widely in molecular and supramolecular chemistry. They have been characterized extensively by ensemble techniques, p...

Self-assembly in chemical synthesis

Abstract: More and more chemists are beginning to realise that the conventional synthetic methodology of making compounds group-by-group or molecule-by-molecule, employing reagents or catalysts to make or break covalent bonds and so manipulate functional groups and transform molecular structures, is insufficient by itself to construct the materials they would like to make in the future. Along its many synthetic trails, nature does not rely upon the inefficient use of protecting groups and the complexity of reagents according to the usual manner and practice of the synthetic organic chemist in a traditional sense. Indeed, one of the keys to the efficient operation of biological systems is their ability to self-assemble,1 self-organise2 and self-replicate.3

Conformational behaviour of medium-sized rings. Part 12. Tri-3-methyltrianthranilide

Abstract: The stepwise synthesis of the N,N′-di- and N,N′,N″-tri-substituted tri-3-methyltrianthranilides (13)–(19) are described. The amino-acid derivatives (34), (38), and (45), which are the key acyclic precursors in the synthesis of the tri-3-methyltrianthranilides, were all prepared from 2-amino-m-toluic acid (22) and 2-nitro-m-toluoyl chloride as starting materials.Tri-3-methyltrianthranilide derivatives with three equivalent N,N′,N″-substituents can exist in either propeller or helical conformations. The N,N′,N″-trimethyl derivative (14) adopts enantiomeric helical conformations in solution and the barrier to ring inversion is 26.8 kcal mol–1. The N,N′,N″-tribenzyl derivative (19) populates both propeller and helical conformations in solution: these two conformational diastereoisomers have been separated by chromatography and isolated as crystalline compounds.Tri-3-methyltrianthranilide derivatives with two or three non-equivalent N,N′,N″-substituents can, in principle, exist in either propeller or three different helical conformations. One of these three helical conformations is specifically populated in deuteriochloroform solution by compounds (13) and (15)–(17). The N,N′-dibenzyl derivative (18) populates the propeller and one helical conformation in solution: two conformational diastereoisomers have been isolated, one as an oil and the other as a crystalline compound.The N,N′-dimethyl-N″-benzyl derivative (15) undergoes spontaneous resolution when it crystallises as a 1 : 1 adduct from toluene. The N-methyl-N′-benzyl derivative (16) also forms a 1 : 1 inclusion compound on crystallisation from toluene. Although this derivative exists as only one conformational diastereoisomer of the helical type in deuteriochloroform solution, two different diastereoisomeric conformations undergo equilibration in hexadeuteriodimethyl sulphoxide with a barrier to interconversion of 16.1 kcal mol–1.

The solid state and solution conformational behaviour of a chiral 30-crown-10 derivative synthesised from 1,4:3,6-dianhydro-D-mannitol; X-ray crystal structure

Abstract: A chiral 30-crown-10 derivative. DD-(2), has been prepared from 1,4:3,6-dianhydro-D-mannitol, D-(1), and shown by X-ray crystallography and dynamic 13C n.m.r. spectroscopy to adopt, in both the solid state and in solution, a ‘face-to-back’ conformation which must undergo substantial change in order to create the hydrophilic cavity necessary for the formation of complexes with Li+, Na+, K+, Rb+, NH4+, MeNH3+, and ButNH3+ ions.

Fast parallel algorithms for short-range molecular dynamics

Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology.

Abstract: Although gold is the subject of one of the most ancient themes of investigation in science, its renaissance now leads to an exponentially increasing number of publications, especially in the context of emerging nanoscience and nanotechnology with nanoparticles and self-assembled monolayers (SAMs). We will limit the present review to gold nanoparticles (AuNPs), also called gold colloids. AuNPs are the most stable metal nanoparticles, and they present fascinating aspects such as their assembly of multiple types involving materials science, the behavior of the individual particles, size-related electronic, magnetic and optical properties (quantum size effect), and their applications to catalysis and biology. Their promises are in these fields as well as in the bottom-up approach of nanotechnology, and they will be key materials and building block in the 21st century. Whereas the extraction of gold started in the 5th millennium B.C. near Varna (Bulgaria) and reached 10 tons per year in Egypt around 1200-1300 B.C. when the marvelous statue of Touthankamon was constructed, it is probable that “soluble” gold appeared around the 5th or 4th century B.C. in Egypt and China. In antiquity, materials were used in an ecological sense for both aesthetic and curative purposes. Colloidal gold was used to make ruby glass 293 Chem. Rev. 2004, 104, 293−346

The Chemistry and Applications of Metal-Organic Frameworks

Abstract: Crystalline metal-organic frameworks (MOFs) are formed by reticular synthesis, which creates strong bonds between inorganic and organic units. Careful selection of MOF constituents can yield crystals of ultrahigh porosity and high thermal and chemical stability. These characteristics allow the interior of MOFs to be chemically altered for use in gas separation, gas storage, and catalysis, among other applications. The precision commonly exercised in their chemical modification and the ability to expand their metrics without changing the underlying topology have not been achieved with other solids. MOFs whose chemical composition and shape of building units can be multiply varied within a particular structure already exist and may lead to materials that offer a synergistic combination of properties.