Conformational Switch of Arylopeptide: Helix–Helix Transition Based on Side Chain Solvation

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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Modeling the Effects of O-sulfonation on the CID of Serine

10.26434/chemrxiv.11783628.v2 ◽

2020 ◽

Author(s):

Kenneth Lucas ◽

George Barnes

Keyword(s):

Sulfo Group ◽

High Energy ◽

Empirical Method ◽

Side Chain ◽

Energy Structure ◽

Direct Dynamics ◽

Theoretical Mass ◽

Intermolecular Proton Transfer ◽

Dynamics Simulations ◽

Semi Empirical

We present the results of direct dynamics simulations and DFT calculations aimed at elucidating the effect of \textit{O}-sulfonation on the collision induced dissociation for serine. Towards this end, direct dynamics simulations of both serine and sulfoserine were performed at multiple collision energies and theoretical mass spectra obtained. Comparisons to experimental results are favorable for both systems. Peaks related to the sulfo group are identified and the reaction dynamics explored. In particular, three significant peaks (m\z 106, 88, and 81) seen in the theoretical mass spectrum directly related to the sulfo group are analyzed as well as major peaks shared by both systems. Our analysis shows that the m\z 106 peaks result from intramolecular rearrangements, intermolecular proton transfer among complexes composed of initial fragmentation products, and at high energy side-chain fragmentation. The \mz 88 peak was found to contain multiple constitutional isomers, including a previously unconsidered, low energy structure. It was also seen that the RM1 semi empirical method was not able to obtain all of the major peaks seen in experiment for sulfoserine. In contrast, PM6 did obtain all major experimental peaks.

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