Side Chain Hydrophobicity Scale using the Tilted Beta-Barrel Protein PagP

SummaryIn 8 patients on no oral intake and with parenteral alimentation, administration of cephalosporins with N-methyl-thiotetrazole side chain (moxalactam, cefamandole), was associated with prolongation of prothrombin time, appearance in the circulation of descarboxy-prothrombin (counter immunoelectrophoresis and echis carinatus assay) and diminution of protein C. Acute administration of 10 mg vitamin Ki was followed by the transient appearance of vitamin K1 2,3-epoxide, indicating an impaired hepatocellular regeneration of vitamin K1 from the epoxide. Impaired hepatic vitamin K1 metabolism, tentatively ascribed to the N-methyl-thiotetrazole group, is one (but possibly not the only) cause of bleeding complications and depression of vitamin K1dependent procoagulants in patients treated with the new class of cephalosporins.

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METABOLISM OF 17α-HYDROXYPROGESTERONE-4-14C-17α-CAPROATE BY HOMOGENATES OF RAT LIVER AND HUMAN PLACENTA

Acta Endocrinologica ◽

10.1530/acta.0.0360511 ◽

1961 ◽

Vol 36 (4) ◽

pp. 511-519 ◽

Cited By ~ 6

Author(s):

Margaret Wiener ◽

Charles I. Lupa ◽

E. Jürgen Plotz

Keyword(s):

Rat Liver ◽

Human Placenta ◽

Steric Hindrance ◽

Placental Tissue ◽

Caproic Acid ◽

Major Product ◽

Side Chain ◽

Anaerobic Conditions ◽

Prolonged Action ◽

Long Acting

ABSTRACT 17α-hydroxyprogesterone-4-14C-17α-caproate (HPC), a long-acting progestational agent, was incubated with homogenates of rat liver and human placenta. The rat liver was found to reduce Ring A of HPC under anaerobic conditions to form allopregnane-3β,17α-diol-20-one-17α-caproate and pregnane-3β,17α-diol-20-one-17α-caproate, the allopregnane isomer being the major product. The caproic acid ester was neither removed nor altered during the incubation. Placental tissue did not attack HPC under conditions where the 20-ketone of progesterone was reduced. It is postulated that this absence of attack on the side chain is due to steric hindrance from the caproate ester, and that this may account for the prolonged action of HPC.

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P450 side-chain cleavage enzyme autoantibodies in canine Addison's disease

Endocrine Abstracts ◽

10.1530/endoabs.31.p329 ◽

2013 ◽

pp. 1-1

Author(s):

Alisdair Boag ◽

Kerry McLaughlin ◽

Mike Christie ◽

Peter Graham ◽

Harriet Syme ◽

...

Keyword(s):

Addison’S Disease ◽

Side Chain ◽

Addison's Disease ◽

Side Chain Cleavage ◽

Chain Cleavage ◽

Cleavage Enzyme

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Influence of Flexible Side-Chains on the Breathing Phase Transition of Pillared Layer MOFs: A Force Field Investigation

10.26434/chemrxiv.11720679.v1 ◽

2020 ◽

Author(s):

Julian Keupp ◽

Johannes P. Dürholt ◽

Rochus Schmid

Keyword(s):

First Principles ◽

Good Accuracy ◽

Field Investigation ◽

Square Lattice ◽

Side Chain ◽

Second Step ◽

Side Chains ◽

Dynamics Simulations ◽

Complex Phenomena ◽

Closed Pore

The prototypical pillared layer MOFs, formed by a square lattice of paddle- wheel units and connected by dinitrogen pillars, can undergo a breathing phase transition by a “wine-rack” type motion of the square lattice. We studied this not yet fully understood behavior using an accurate first principles parameterized force field (MOF-FF) for larger nanocrystallites on the example of Zn 2 (bdc) 2 (dabco) [bdc: benzenedicarboxylate, dabco: (1,4-diazabicyclo[2.2.2]octane)] and found clear indi- cations for an interface between a closed and an open pore phase traveling through the system during the phase transformation [Adv. Theory Simul. 2019, 2, 11]. In conventional simulations in small supercells this mechanism is prevented by periodic boundary conditions (PBC), enforcing a synchronous transformation of the entire crystal. Here, we extend this investigation to pillared layer MOFs with flexible side-chains, attached to the linker. Such functionalized (fu-)MOFs are experimen- tally known to have different properties with the side-chains acting as fixed guest molecules. First, in order to extend the parameterization for such flexible groups, 1a new parametrization strategy for MOF-FF had to be developed, using a multi- structure force based fit method. The resulting parametrization for a library of fu-MOFs is then validated with respect to a set of reference systems and shows very good accuracy. In the second step, a series of fu-MOFs with increasing side-chain length is studied with respect to the influence of the side-chains on the breathing behavior. For small supercells in PBC a systematic trend of the closed pore volume with the chain length is observed. However, for a nanocrystallite model a distinct interface between a closed and an open pore phase is visible only for the short chain length, whereas for longer chains the interface broadens and a nearly concerted trans- formation is observed. Only by molecular dynamics simulations using accurate force fields such complex phenomena can be studied on a molecular level.

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Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

10.26434/chemrxiv.11481834.v1 ◽

2019 ◽

Author(s):

Nobutaka Fujieda ◽

Miho Yuasa ◽

Yosuke Nishikawa ◽

Genji Kurisu ◽

Shinobu Itoh ◽

...

Keyword(s):

Michael Addition ◽

In Silico ◽

Addition Reaction ◽

Single Point ◽

Point Mutations ◽

Unsaturated Ketone ◽

Michael Addition Reaction ◽

Beta Barrel ◽

Cupin Superfamily ◽

Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

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