New monomers, 5'-O-DMT-deoxyribonucleoside 3'-O-(2-thio-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s, were prepared and used for the stereocontrolled synthesis of PS−Oligos via oxathiaphospholane approach. These monomers their 2-oxo analogues "chimeric" constructs (PS/PO−Oligos) possessing phosphate P-stereodefined phosphorothioate internucleotide linkages. The yield a single coupling step is approximately 92−95%, resulting oligomers are free nucleobase- sugar-phosphorothioate...

Addition of α-phosphonate carbanions to (S)-sulfinimines 1 affords N-sulfinyl β-aminophosphonates 2 in a diastereoisomeric ratio from 5:1 10:1; the major diastereoisomers 2, after separation, are converted corresponding 3 or (+)-β-amino-β-phenylethane phosphonic acid 4, whose absolute configuration was established as (R) by X-ray crystallography.

Monocyte chemotactic protein 2 (MCP-2) is a CC chemokine that utilizes multiple cellular receptors to attract and activate human leukocytes. MCP-2 potent inhibitor of HIV-1 by virtue its high-affinity binding the receptor CCR5, one major coreceptors for HIV-1. Although few structures chemokines have been reported, none these was determined with N-terminal pyroglutamic acid residue (pGlu1) complete C-terminus. pGlu1 essential activity MCP-2. Recombinant has Gln1 at N terminus, 12−15% which...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereochemistry of base-catalyzed ring opening 1,3,2-oxathiaphospholanes. Absolute configuration 2-{N-[(Rc)-1-(.alpha.-naphthyl)ethyl]amino}-2-thiono-1,3,2-oxathiaphospholanes and O,S-dimethyl N-[(Rc)-1-(.alpha.-naphthyl)ethyl]phosphoramidothioatesB. Uznanski, A. Grajkowski, B. Krzyzanowska, Kazmierkowska, W. J. Stec, M. Wieczorek, BlaszczykCite this: Am. Chem. Soc. 1992, 114, 26, 10197–10202Publication Date (Print):December 1, 1992Publication...

Two variants of human class pi glutathione (GSH) S-transferase 1-1 with either isoleucine or valine in position 104 (hGSTP1-1[I104] and hGSTP1-1[V104]) have distinct activity toward (+)-anti-7, 8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. To elucidate their structure-function relationship, we determined the crystal structures two complex GSBpd, GSH conjugate (+)-anti-BPDE, at 2.1 2.0 A resolution, respectively. The reveal that residue xenobiotic substrate-binding...

During crystallization screenings of commercially available hydrolytic enzymes, the new, hexagonal crystal form CAL-B, has been discovered and hereby reported. The NAG molecules, which were closing glycosylation site in orthorhombic form, structure make open. It is unknown whether opening by 'lid' could be related to active center enzyme upon substrate binding product release.

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), leading biosynthesis folate cofactors. Like other enzymes in pathway, HPPK is an ideal target for development antimicrobial agents because enzyme essential microorganisms but absent human and animals. Three bisubstrate analogues have been synthesized characterized by biochemical X-ray crystallographic analyses. All three consist a pterin,...

The crystal structure of <i>Escherichia coli</i> 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) in complex with MgADP has been determined at 1.5-Å resolution a crystallographic <i>R</i> factor 0.191. solution HPPK Mg²⁺ and β,γ-methyleneadenosine 5′-triphosphate (MgAMPPCP) using simulated annealing protocol 3,523 experimental NMR restraints. root mean square deviation the ensemble 20 refined conformers that represent from coordinate set derived them is 0.74 ± 0.26 Å for...

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HMDP). Because HPPK is essential for microorganisms but absent human and animals, enzyme an excellent target developing antimicrobial agent. Thermodynamic analysis shows that Mg2+ important not only binding nucleotides also HMDP. Transient kinetic a step or steps after chemical transformation are rate-limiting in reaction catalyzed by HPPK. The...

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), first reaction in folate biosynthetic pathway. Arginine residues 82 and 92, strictly conserved 35 HPPK sequences, play dynamic roles catalytic cycle of enzyme. At 0.89-Å resolution, two distinct conformations are observed for each crystal structure wild-type complex with HP variants, Mg2+ ions, an analogue. Structural information suggests that...

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphoryl group from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP) following an ordered bi−bi mechanism with as first substrate. The rate-limiting step reaction is product release, and complete active center assembled sealed only upon binding both HP. assembly involves large conformational changes in three catalytic loops, among which loop 3 undergoes most dramatic unusual changes. To investigate roles...

The complete desymmetrization of optically inactive meso-tartaric acid with (+)-camphor in the presence trimethyl orthoformate is key to synthesis both enantiomers cyclopentenoid isoterrein enantiomerically pure form.

Abstract The Candida antarctica lipase (CAL‐B)‐catalyzed acetylation of racemic 2‐hydroxymethylphenyl(methyl)phenylphosphine oxide, performed in diethyl ether, led to kinetic resolution with an unusually high enantioselectivity ( E =3000). CAL‐B‐mediated desymmetrization prochiral bis(2‐hydroxymethylphenyl)methylphosphine oxide gave, via its enantioselective monoacetylation, the corresponding monoacetate 80% yield and ee &gt;98%. latter transformation allowed us efficiently transform...

Abstract We have developed new approaches to diverse enantiopure aminophosphonic acids by using enantiomeric ( S )‐ N ‐( p ‐tolylsulfinyl)cinnamaldimine 1 ) as a single starting material. The synthetic strategy is based on highly diastereoselective addition reaction of phosphite anion or α‐phosphonate carbanion sulfinimine followed isolation the major diastereoisomeric α‐amino‐ β‐amino adducts and their further conversion desired targets through proper transformation cinnamylidene moiety....

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Modeling, X-ray Diffraction, and 13C,77Se CP/MAS NMR Studies of Bis(2,3,4,6-tetra-O-acetyl-.beta.-D-glucopyranosyl) Diselenide DisulfideMarek J. Potrzebowski, Maria Michalska, Jaroslaw Blaszczyk, Michal W. Wieczorek, Wlodzimierz Ciesielski, Slawomir Kazmierski, January PluskowskiCite this: Org. Chem. 1995, 60, 10, 3139–3148Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1...

Methoxycarbonylmethyl carboxymethyl sulfoxide 3 and 2-acetoxyethyl 2-hydroxyethyl 4 have been obtained in high enantiomeric purity by the enzyme-mediated hydrolysis of corresponding prochiral sulfinyldicarboxylates 1 2. The R configuration has assigned to enantiomerically pure (-)-3, [α]D 20 -20, X-ray analysis.

The roles of a pair conserved positively charged residues R82 and R92 at catalytic loop Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) have been investigated by site-directed mutagenesis biochemical analysis. In the structure HPPK in complex with ATP (HP) analogue, guanidinium group forms two hydrogen bonds α-phosphate that β-phosphate. α,β-methyleneadenosine triphosphate (AMPCPP, an analogue) HP, has no direct interaction AMPCPP α-phosphate. Substitution alanine...

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate-biosynthetic pathway and essential for microorganisms but absent from mammals. HPPK catalyzes Mg2+-dependent pyrophosphoryl transfer ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). Previously, three-dimensional structures of Escherichia coli (EcHPPK) have been determined at almost every stage its catalytic cycle reaction mechanism has established. Here, crystal structure Yersinia pestis (YpHPPK) complex...