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B M Foxman

Publications and source records attributed to B M Foxman.

9 recordsLinked to original sources
PubMed2001

New open frameworks based on metal pyridylphosphonates.

A family of new 1D, 2D, and 3D coordination networks based on metal-pyridylphosphonates have been synthesized under hydro(solvo)thermal conditions. Zn(3-pyridylphosphonate)(bromide), 1, adopts a 1D ladder structure, while Co(4-pyridylphosphonate)(H(2)O)(3), 2, adopts a 2D grid structure. [Cu(2)(4-pyridylphosphonate)(2)]-2H(2)O, 3, [Cd(3-pyridylphosphonate)(2)]-DMSO, 4, Cd(4-pyridylphosphonate)(2), 5, and Cd(ethyl 4-pyridylphosphonate)(2), 6, all adopt 3D framework structures. While 3 possesses open channels that are occupied by water molecules, 4 exhibits cavities that accommodate DMSO guest molecules. The present work demonstrates that interesting open frameworks can be readily synthesized on the basis of metal pyridylphosphonates. Crystal data for 1: monoclinic space group C2/c; a = 15.267(4), b = 11.903(2), c = 10.380(2) A; beta = 98.68(2) degrees; Z = 8. Crystal data for 2: monoclinic space group P2(1)/c; a = 9.634(12), b = 7.611(9), c = 11.901(1) A; beta = 97.830(2) degrees; Z = 4. Crystal data for 3: triclinic spacegroup P one macro; a = 7.464(8), b = 9.203(1), c = 11.602(2) A; alpha = 100.289(1) degrees; beta = 104.532(1) degrees, gamma = 94.569(1) degrees; Z = 2. Crystal data for 4: tetragonal space group I4(1)/a; a = 15.114(2), b = 15.114(2), c = 13.128(3) A; Z = 8. Crystal data for 5: monoclinic space group P2(1)/c; a = 8.344(2), b = 10.589(2), c = 14.384(3) A; beta = 91.77(3) degrees; Z = 4. Crystal data for 6: monoclinic space group P2(1)/n; a = 5.606(1), b = 11.198(1), c = 14.176(2) A; beta = 94.518(1) degrees; Z = 2.

Journal Article↗
PubMed2000

Comparison of the effects of 5- and 6-HOAt on model peptide coupling reactions relative to the cases for the 4- and 7-Isomers.

Synthesis of 5- and 6-HOAt has completed the full set of the four HOAt isomers derived from HOBt by insertion of a single nitrogen atom in the benzenoid nucleus. Comparison of the reactivity of all four isomers in model peptide coupling reactions has confirmed the unique character of the 7-isomer in promoting selectivity and maintaining configuration at the reactive carboxylic acid residue.

Aniline Compounds↗
PubMed2000

Total syntheses of (+/-)-anchinopeptolide D and (+/-)-cycloanchinopeptolide D.

The first synthesis of (+/-)-anchinopeptolide D (4) has been accomplished in seven steps in 10% overall yield from octopamine hydrochloride (17), N-(Boc)glycine (16), and 5-amino-2-hydroxypentanoic acid (22). The key step is the aldol dimerization and hemiaminal formation of alpha-keto amide 26, which gives primarily protected anchinopeptolide D 27 under kinetically controlled conditions. Cycloanchinopeptolide D (31) has been prepared by the unprecedented head-to-head photodimerization of the two hydroxystyrylamides of 4 using the hydrophobic effect in water to force the two side chains into close proximity so that [2 + 2] cycloaddition is faster than trans to cis double bond isomerization. Coupling of amine 21 with pyroglutamic acid affords the naturally occurring tripeptide 35, which had been assigned glutamic acid structure 34.

Alkaloids↗
PubMed1996

A search for the ideal type I beta-turn.

In 1968 C. Venkatachalam (Biopolymers, Vol. 6, pp. 1425-1436) predicted the ideal forms of beta-turns (type I, type II, etc.) based entirely on theoretical calculations. Subsequently, over a thousand x-ray structures of different globular proteins have been analyzed, with results suggesting that the most important form among the hairpin conformers is the type I beta-turn. For the latter type of hairpin conformation, the original computations had predicted phi i+I = -60 degrees, psi i+1 = -30 degrees, phi i+2 = -90 degrees, and psi i +2 = 0 degrees as backbone torsion angle values, and these have been used from that time as reference values for the identification of the type I beta-turn. However, it has never been clarified whether these "ideal" backbone torsion angle values exist in real structures, or whether these torsion angles are only "theoretical values." Using the most recent release of the Protein Data Bank (1994), a survey has been made to assign amino acid pairs that approach the ideal form of the type I beta-turn. The analysis resulted in four sequences where the deviation from ideal values for any main-chain torsion angles was less than 2 degrees. In order to determine whether such a backbone fold is possible only in proteins owing to fortuitous cooperation of different folding effects, or whether it occurs even in short peptides, various attempts have been made to design the optimal amino acid sequence. Such a peptide model compound adopting precisely the predicted torsion angle values [phi i+1 = -60 degrees, psi i +1 = -30 degrees, phi i +2 = -90 degrees, and psi i+2 = 0 degrees] could provide valuable information. The solid state conformation of cyclo[(delta)Ava-Gly-Pro-Thr(OtBu)-Gly] reported herein, incorporating the -Pro-Thr- subunit, yields values suggesting that the "ideal" type I beta-turn is even possible for a peptide where there are no major environmental effects present.

Amino Acid Sequence↗
PubMed1994

Chloroketone hydrolysis by chymotrypsin and N-methylhistidyl-57-chymotrypsin: implications for the mechanism of chymotrypsin inactivation by chloroketones.

We have examined the reaction of N-(benzyloxycarbonyl)-L-alanyl-L-glycyl-L-phenylalanyl chloromethyl ketone (ZAGFCMK) with chymotrypsin (Cht) and have found that, in addition to irreversible alkylation of the enzyme, some of the corresponding hydroxymethyl ketone is produced. For each molecule of hydroxy ketone formed, 3.6 molecules of chymotrypsin are inactivated. Chloroketone hydrolysis is also observed with chymotrypsin methylated at N-3 of the active site histidine (MeCht). The hydrolysis proceeds slowly (k = 0.14 min-1). Alkylation of the modified enzyme was not observed. An initial burst of free chloride is detected during the MeCht-catalyzed hydrolysis. The magnitude of the chloride burst is proportional to the enzyme concentration in an approximate 1:1 stoichiometry and indicates a relatively rapid chloride-releasing step which gives rise to an intermediate which is more slowly converted to hydroxy ketone. We have also investigated both the solution and MeCht-mediated hydrolysis of the S isomer of N-acetyl-L-alanyl-L-phenylalanyl chloroethyl ketone (S-AcAFCEK). We have concluded that the nonenzymatic hydrolysis proceeds with inversion of configuration at the stereocenter, while the enzymatic process occurs with retention of configuration. The two nucleophilic displacements attending the MeCht-mediated hydrolysis of S-AcAFCEK imply the formation of an intermediate, possibly of an epoxy ether, formed by internal displacement of the chloride by the oxyanion of the initially generated enzyme-chloroketone hemiketal adduct.

Alkylation↗
PubMed1992

How reverse turns may mediate the formation of helical segments in proteins: an x-ray model.

The three-dimensional structure of a protein is the assembly of different secondary structural elements, such as alpha-helices, beta-pleated sheets, and beta-turns. Although the conformation of hundreds of proteins has been elaborated in the solid state, only a vague understanding of the mechanism of their conformational folding is known. One facet of this topic is the conformational interconversion of one or more beta-turns to a helical structure (and vice versa), which may also be related to the formation of helix-turn-helix motifs often observed in globular proteins. Based on a comprehensive structural analysis of proteins, Sundaralingam and Sekharudu [Sundaralingam, M. & Sekharudu, Y. C. (1989) Science 244, 1333-1337] previously suggested that "structure-water" molecules in proteins may mediate such a conformational change. An x-ray crystal structure determination of t-butoxycarbonyl (Boc)-Val-Ser-NHCH3 reveals (i) an ideal type I beta-turn backbone conformation and (ii) a hydrogen-bond network more typical of an alpha-helix than a beta-turn conformation. The molecular packing of this simple beta-turn model reported here provides a plausible and simple alternative of how a beta-turn-like conformation may serve as a conformational template for helical-structure formation (and vice versa) during the folding procedure.

Hydrogen Bonding↗
PubMed1982

DL-threo-beta-Fluoroaspartate and DL-threo-beta-fluoroasparagine: selective cytotoxic agents for mammalian cells in culture.

Absolute configuration assignments have been made for the diastereomers of DL-beta-fluoroaspartate by X-ray analysis. The cytotoxicity of these isomers against various mammalian cells was examined. DL-threo-beta-Fluoroaspartate shows selective cytotoxicity. Growth of the most sensitive cells is completely inhibited by 13 micrometers DL-threo-beta-fluoroaspartate in the presence of 100 micrometers L-aspartate, a component of the culture medium. A difference in the rate of transport of DL-beta-fluoroaspartate among the cells studied is an important factor determining cell specificity. For those cells that are sensitive to DL-beta-fluoroaspartate, the threo isomer is, in all cases, more potent than the erythro isomer. Radioactivity derived from L-threo-beta-fluoro[14C]aspartate is incorporated into proteins at a rate comparable to the rate of incorporation from L-[14C]aspartate. We synthesized DL-threo-beta-fluoroasparagine. This compound is also cytotoxic but less specific and less potent than DL-threo-beta-fluoroaspartate. However, the cell specificity can be enhanced in the presence of 1 mM L-aspartate, which can protect some cells but not others from the cytotoxic effects of DL-threo-beta-fluoroasparagine. Jensen sarcoma cells, which require asparagine, are not protected by L-aspartate. Therefore, a combination of L-aspartate and DL-threo-beta-fluroasparagine can be used to inhibit specifically the growth of asparagine-requiring tumors.

Amino Acids↗