The inhibition of chymotrypsin A4 with a homologous series of chloromethyl ketone reagents

1970 ◽  
Vol 48 (3) ◽  
pp. 364-375 ◽  
Author(s):  
Kenneth J. Stevenson ◽  
Lawrence B. Smillie
Keyword(s):  
Binding Site ◽  
Homologous Series ◽  
Imidazole Ring ◽  
The Other ◽  
Chloromethyl Ketone ◽  
Basic Group ◽  
Acid Hydrolysate ◽  
Other Hand ◽  
Hydrophobic Binding ◽  
Chymotrypsin A

The inactivation of chymotrypsin A4 (CHT-A4) by a homologous phenylalkyl series of bifunctional reagents, viz. phenyl chloromethyl ketone (PCK), benzyl chloromethyl ketone (BCK), and β-phenylethyl chloromethyl ketone (βPECK) (C6H5 [CH2]n COCH2Cl where n = 0, 1, or 2), has been investigated. The inactivation of CHT-A4 by PCK has been shown to be essentially pH independent whereas inactivation by BCK and βPECK appears to be dependent on a basic group of pK 6.0–6.3. PCK has been shown to inhibit CHT-A4 by virtue of the complete S-alkylation of methionine-192. BCK and βPECK, on the other hand, inactivate CHT-A4 through a combination of partial S-alkylation of methionine-192 (0.2 and 0.3 residue, respectively) and partial alkylation of histidine-57 (0.2 and 0.4 residue, respectively). Identification of the particular residue alkylated was obtained through the isolation and analysis of alkylated and oxidized peptic peptides obtained from the alkylated CHT-A4 by the diagonal peptide ionophoresis technique.The initial site of alkylation of BCK and βPECK on the imidazole ring of histidine-57 has not been identified. However, a unique histidine derivative has been isolated from the acid hydrolysate of oxidized histidine-57 peptide from CHT-A4–βPECK and is suggested to be 2(or 4)-hydroxymethylhistidine.On the basis of the present studies on the phenylalkyl series and on studies reported earlier on a phenylalkylamido halomethyl ketone series of bifunctional reagents which alkylates only methionine in CHT-A4, it has been suggested that alkylation of histidine by members of the phenylalkyl series is primarily a result of binding to the hydrophobic binding site of CHT-A4 rather than binding to the acylamido binding site as is suggested to be the case for the phenylalkylamido series.

Selective guest recognition by a metallo-organic phthalocyanine-based host

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1570-1575
Author(s):  
Ettore Fazio ◽  
M. Jesús Vicente-Arana ◽  
M. Teresa Alonso ◽  
Tomás Torres ◽  
Gema de la Torre
Keyword(s):  
Internal Surface ◽  
Imidazole Ring ◽  
Coordination Bond ◽  
The Other ◽  
Other Hand

In this manuscript, we have studied the selectivity in the complexation of fullerene species by a Fe[Formula: see text]Pc[Formula: see text] metallo-organic helicate (1) assembled using a bidentate phthalocyanine (Pc) as ligand. The large aromatic internal surface of this helicate shows a strong selectivity towards the encapsulation of C[Formula: see text] from a mixture of C[Formula: see text] and C[Formula: see text]. On the other hand, a bisimidazole-containing naphthalenediimide was used to perform guest exchange experiments over [fullerene [Formula: see text] 1] complexes, taking advantage of the strong coordination bond of the imidazole ring to the Zn centers in the Pc cavity.

scholarly journals THE POTENTIAL AND RESPIRATION OF FROG SKIN

1937 ◽  
Vol 20 (3) ◽  
pp. 433-447 ◽  
Author(s):  
Eric Ponder ◽  
John Macleod
Keyword(s):  
Homologous Series ◽  
Bile Salts ◽  
Frog Skin ◽  
The Other ◽  
Entire System ◽  
O2 Consumption ◽  
Other Hand

Measurements of the O2 consumption and of the potential of frog skin, made under comparable conditions, show that the homologous carbamates (ethyl, propyl, butyl, and amyl) reduce both the O2 consumption and the potential, but not in a similar manner. In this respect, the effect of the carbamates is like the effect of reduction in O2 tension. The simple lysins (saponin and the bile salts), on the other hand, abolish the potential without reducing the O2 consumption at all. Irrespective of whether one considers the concentration of carbamate in the entire system or the amount of carbamate adsorbed by the frog skin, Traube's rule relating the effect of a carbamate to its position in the homologous series does not seem to apply.

The Inhibition of chymotrypsins A4 and B with chloromethyl ketone reagents

1968 ◽  
Vol 46 (11) ◽  
pp. 1357-1370 ◽  
Author(s):  
Kenneth J. Stevenson ◽  
Lawrence B. Smillie
Keyword(s):  
Aromatic Ring ◽  
Histidine Residue ◽  
Straight Chain ◽  
Isolation And Identification ◽  
Chloromethyl Ketone ◽  
Basic Group ◽  
Chymotrypsin B ◽  
Chymotrypsin A

The inactivation of chymotrypsin A4 and B by the bifunctional reagents L-(1-tosylamido-2-phenyl) ethyl chloromethyl ketone (L-TPCK) and phenoxymethyl chloromethyl ketone (PMCK) has been investigated. The rate of inactivation of chymotrypsin A4 with both reagents as a function of pH has been shown to be dependent on a basic group of pK = 6.3–6.5. Chymotrypsin B inactivation appears to be dependent on a basic group with a somewhat lower pK. For each enzyme the reaction with both reagents is associated with the loss of a single histidine residue. By the isolation and identification of 3-carboxymethylhistidine from the alkylated and oxidized peptic histidine-57 peptides, it has been concluded that both enzymes are alkylated at the nitrogen-3 position of histidine-57 by L-TPCK and PMCK. Evidence for the submolar alkylation of methionine-192 of chymotrypsin A4 by L-TPCK, PMCK, D-(1-tosylamido-2-phenyl) ethyl chloromethyl ketone (D-TPCK), and N-methyl-L-TPCK is presented. There is no alkylation of the histidine of chymotrypsin A4 by D-TPCK or.N-methyl-L-TPCK.From a comparison of the structures of a number of reagents known to alkylate chymotrypsin A4, it has been concluded that the alkylation of methionine-192 is nonspecific and relatively independent of any defined stereochemistry of the reagent employed. To date the alkylation of histidine-57 has been shown to occur only with haloketones, and is dependent on the distance between the haloketone and the aromatic ring when the latter is present. Although the presence of an asymmetric α-carbon and acylamido group in straight-chain reagents is unnecessary for histidine alkylation, these must be of the L configuration if present.

Interaction of platelets with liposomes containing dodecapeptide sequence from fibrinogen

2004 ◽  
Vol 91 (06) ◽  
pp. 1158-1167 ◽  
Author(s):  
Chikaho Toma ◽  
Takako Nishiya
Keyword(s):  
Platelet Aggregation ◽  
Binding Site ◽  
Synthetic Peptide ◽  
Surface Density ◽  
The Other ◽  
Interaction Site ◽  
Ligand Affinity ◽  
Rgd Sequence ◽  
Activated Platelets ◽  
Other Hand

SummaryLiposomes with a covalently bound synthetic peptide containing the dodecapeptide sequence HHLGGAKQAGDV, the putative platelet interaction site at γ400-411 of fibrinogen (dodecapeptide-liposomes), were prepared. These liposomes enhanced platelet aggregation and specifically adhered to platelets activated on the collagen surface. Dodecapeptide-liposomes released encapsulated materials upon interacting with platelets activated on the collagen surface.The rate of content release was dependent on the peptide surface density, indicating that the interaction between the dodecapeptide-liposomes and platelets activated on the collagen surface induces clustering of the surfacecoupled ligands at the binding site on the receptor matrix to facilitate release of the internal contents through the liposome membranes. The level of lipid mixing between the dodecapeptide-liposomes and platelets activated on the collagen surface was relatively low, however it was increased in liposome preparations containing octa-arginine, the (R)8GDV sequence, while content release was maintained at the same level as that of the dodecapeptide-liposomes. The level of content release and lipid mixing for liposome preparations containing the RGD sequence as a ligand (RGD-liposomes) upon interacting with platelets activated on the collagen surface was extremely low. Both the level of the content release and lipid mixing, however, were enhanced in liposome preparations containing octa-arginine, the (R)8RGD sequence. Dodecapeptide-liposomes and RGD-liposomes were not internalized by activated platelets. On the other hand, liposomes containing (R)8PPQ, (R)8RGD, or (R)8GDV were internalized by activated platelets, and the extent of internalization was inversely related to ligand affinity to the target.

scholarly journals Non-Competitive Inhibition of Acetylcholinesterase by Bromotyrosine Alkaloids

2014 ◽  
Vol 9 (11) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Opeyemi J. Olatunji ◽  
Akintayo L. Ogundajo ◽  
Ibrahim A. Oladosu ◽  
Kanokwan Changwichit ◽  
Kornkanok Ingkaninan ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Binding Sites ◽  
Competitive Inhibition ◽  
The Other ◽  
Inhibiting Activity ◽  
Active Compounds ◽  
Other Hand ◽  
Hydrophobic Binding ◽  
Mcf 7

Fifteen bromotyrosine-derived alkaloids were isolated from the sponge Pseudoceratina cf. purpurea. The acetylcholinesterase-inhibiting activity of all the isolated compounds were examined; to purealidin Q, isoanomoian A, aplyzanzine A, and aplysamine 2 were active with IC50 values of 1.2, 70, 104, and 1.3 μM, respectively. On the other hand, antiproliferative activity against MCF-7 cells of aerophobin 1 gave an IC50 value of 0.8 μM. The Michaelis-Menten plots of the active alkaloids indicated that all the four compounds inhibited acetylcholinesterase in a non-competitive manner. The structures of the active compounds suggested that the N, N-dimethylaminopropyloxydibromotyramine moiety may play an important role in the enzyme-inhibiting activity, presumably on the anionic and hydrophobic binding sites.

A study of cometary eruptions through OH radio-lines

1999 ◽  
Vol 173 ◽  
pp. 249-254
Author(s):  
A.M. Silva ◽  
R.D. Miró
Keyword(s):  
Short Duration ◽  
Growth Curves ◽  
The Other ◽  
Initial Mass ◽  
Radio Lines ◽  
Other Hand ◽  
Sudden Rise

AbstractWe have developed a model for theH2OandOHevolution in a comet outburst, assuming that together with the gas, a distribution of icy grains is ejected. With an initial mass of icy grains of 108kg released, theH2OandOHproductions are increased up to a factor two, and the growth curves change drastically in the first two days. The model is applied to eruptions detected in theOHradio monitorings and fits well with the slow variations in the flux. On the other hand, several events of short duration appear, consisting of a sudden rise ofOHflux, followed by a sudden decay on the second day. These apparent short bursts are frequently found as precursors of a more durable eruption. We suggest that both of them are part of a unique eruption, and that the sudden decay is due to collisions that de-excite theOHmaser, when it reaches the Cometopause region located at 1.35 × 105kmfrom the nucleus.

Closing the GAP—A 5Å Scanning Microscope

1969 ◽  
Vol 27 ◽  
pp. 6-7
Author(s):  
A. V. Crewe
Keyword(s):  
Normal Form ◽  
The Other ◽  
Resolving Power ◽  
Scanning Microscope ◽  
Conventional Microscope ◽  
Other Hand ◽  
Closing The Gap ◽  
Thermal Sources ◽  
Better Than ◽  
Transmission Microscope

We have become accustomed to differentiating between the scanning microscope and the conventional transmission microscope according to the resolving power which the two instruments offer. The conventional microscope is capable of a point resolution of a few angstroms and line resolutions of periodic objects of about 1Å. On the other hand, the scanning microscope, in its normal form, is not ordinarily capable of a point resolution better than 100Å. Upon examining reasons for the 100Å limitation, it becomes clear that this is based more on tradition than reason, and in particular, it is a condition imposed upon the microscope by adherence to thermal sources of electrons.

Life Beyond 1MeV

1980 ◽  
Vol 38 ◽  
pp. 30-33
Author(s):  
K.H. Westmacott
Keyword(s):  
Electron Microscopy ◽  
Past Experience ◽  
The Other ◽  
Good Case ◽  
Other Hand ◽  
The U.S

Life beyond 1MeV – like life after 40 – is not too different unless one takes advantage of past experience and is receptive to new opportunities. At first glance, the returns on performing electron microscopy at voltages greater than 1MeV diminish rather rapidly as the curves which describe the well-known advantages of HVEM often tend towards saturation. However, in a country with a significant HVEM capability, a good case can be made for investing in instruments with a range of maximum accelerating voltages. In this regard, the 1.5MeV KRATOS HVEM being installed in Berkeley will complement the other 650KeV, 1MeV, and 1.2MeV instruments currently operating in the U.S. One other consideration suggests that 1.5MeV is an optimum voltage machine – Its additional advantages may be purchased for not much more than a 1MeV instrument. On the other hand, the 3MeV HVEM's which seem to be operated at 2MeV maximum, are much more expensive.

Can the Academic Self-Concept be Positive and Realistic?

2005 ◽  
Vol 19 (3) ◽  
pp. 129-132 ◽  
Author(s):  
Reimer Kornmann
Keyword(s):  
Academic Performance ◽  
Opposite Effect ◽  
Self Esteem ◽  
Point Of View ◽  
The Other ◽  
Self Concept ◽  
High Ability ◽  
Self Image ◽  
Other Hand

Summary: My comment is basically restricted to the situation in which less-able students find themselves and refers only to literature in German. From this point of view I am basically able to confirm Marsh's results. It must, however, be said that with less-able pupils the opposite effect can be found: Levels of self-esteem in these pupils are raised, at least temporarily, by separate instruction, academic performance however drops; combined instruction, on the other hand, leads to improved academic performance, while levels of self-esteem drop. Apparently, the positive self-image of less-able pupils who receive separate instruction does not bring about the potential enhancement of academic performance one might expect from high-ability pupils receiving separate instruction. To resolve the dilemma, it is proposed that individual progress in learning be accentuated, and that comparisons with others be dispensed with. This fosters a self-image that can in equal measure be realistic and optimistic.

Stories and the Self

2020 ◽  
Vol 32 (2) ◽  
pp. 47-58 ◽  
Author(s):  
Stefan Krause ◽  
Markus Appel
Keyword(s):  
Meta Analysis ◽  
The Self ◽  
The Other ◽  
Lower Degree ◽  
Contrast Effects ◽  
Self Perception ◽  
Self Perceptions ◽  
Other Hand ◽  
The One ◽  
Implicit And Explicit

Abstract. Two experiments examined the influence of stories on recipients’ self-perceptions. Extending prior theory and research, our focus was on assimilation effects (i.e., changes in self-perception in line with a protagonist’s traits) as well as on contrast effects (i.e., changes in self-perception in contrast to a protagonist’s traits). In Experiment 1 ( N = 113), implicit and explicit conscientiousness were assessed after participants read a story about either a diligent or a negligent student. Moderation analyses showed that highly transported participants and participants with lower counterarguing scores assimilate the depicted traits of a story protagonist, as indicated by explicit, self-reported conscientiousness ratings. Participants, who were more critical toward a story (i.e., higher counterarguing) and with a lower degree of transportation, showed contrast effects. In Experiment 2 ( N = 103), we manipulated transportation and counterarguing, but we could not identify an effect on participants’ self-ascribed level of conscientiousness. A mini meta-analysis across both experiments revealed significant positive overall associations between transportation and counterarguing on the one hand and story-consistent self-reported conscientiousness on the other hand.

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