scholarly journals Supracrystallographic resolution of interactions contributing to enzyme catalysis by use of natural structural variants and reactivity-probe kinetics

1988 ◽  
Vol 256 (2) ◽  
pp. 543-558 ◽  
Author(s):  
K Brocklehurst ◽  
S M Brocklehurst ◽  
D Kowlessur ◽  
M O'Driscoll ◽  
G Patel ◽  
...  
Keyword(s):  
Enzyme Catalysis ◽  
Amide Bond ◽  
Side Chain ◽  
Pka Value ◽  
Catalytic Sites ◽  
Rate Maximum ◽  
Rate Minimum ◽  
The Common ◽  
Profile Change ◽  
Macroscopic Pka

1. The influence on the reactivities of the catalytic sites of papain (EC 3.4.22.2) and actinidin (3.4.22.14) of providing for interactions involving the S1-S2 intersubsite regions of the enzymes was evaluated by using as a series of thiol-specific two-hydronic-state reactivity probes: n-propyl 2-pyridyl disulphide (I) (a ‘featureless’ probe), 2-(acetamido)ethyl 2′-pyridyl disulphide (II) (containing a P1-P2 amide bond), 2-(acetoxy)ethyl 2′-pyridyl disulphide (III) [the ester analogue of probe (II)] and 2-carboxyethyl 2′-pyridyl disulphide N-methylamide (IV) [the retroamide analogue of probe (II)]. Syntheses of compounds (I), (III) and (IV) are reported. 2. The reactivities of the two enzymes towards the four reactivity probes (I)-(IV) and also that of papain towards 2-(N'-acetyl-L-phenylalanylamino)ethyl 2′-pyridyl disulphide (VII) (containing both a P1-P2 amide bond and an L-phenylalanyl side chain as an occupant for the S2 subsite), in up to four hydronic (previously called protonic) states, were evaluated by analysis of pH-dependent stopped-flow kinetic data (for the release of pyridine-2-thione) by using an eight-parameter rate equation [described in the Appendix: Brocklehurst & Brocklehurst (1988) Biochem. J. 256, 556-558] to provide pH-independent rate constants and macroscopic pKa values. The analysis reveals the various ways in which the two enzymes respond very differently to the binding of ligands in the S1-S2 intersubsite regions despite the virtually superimposable crystal structures in these regions of the molecules. 3. Particularly striking differences between the behaviour of papain and that of actinidin are that (a) only papain responds to the presence of a P1-P2 amide bond in the probe such that a rate maximum at pH 6-7 is produced in the pH-k profile in place of the rate minimum, (b) only in the papain reactions does the pKa value of the alkaline limb of the pH-k profile change from 9.5 to approx. 8.2 [the value characteristic of a pH-(kcat./Km) profile] when the probe contains a P1-P2 amide bond, (c) only papain reactivity is affected by two positively co-operative hydronic dissociations with pKI congruent to pKII congruent to 4 and (d) modulation of the reactivity of the common -S(-)-ImH+ catalytic-site ion-pair (Cys-25/His-159 in papain and Cys-25/His-162 in actinidin) by hydronic dissociation with pKa approx. 5 is more marked and occurs more generally in reactions of actinidin than is the case for papain reactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Synthesis of new cyclopeptide analogues of the miuraenamides

2021 ◽  
Vol 18 ◽  
Author(s):  
Sarah Kappler ◽  
Andreas Siebert ◽  
Uli Kazmaier
Keyword(s):  
Natural Products ◽  
Biological Properties ◽  
Amide Bond ◽  
Side Chain ◽  
Aromatic Side Chain ◽  
Highly Active ◽  
C Terminus ◽  
Terminal Amino ◽  
High Cytotoxicity ◽  
Derivatives Of

Introduction: Miuraenamides belong to marine natural compounds with interesting biological properties. Materials and Methods: They initiate polymerization of monomeric actin and therefore show high cytotoxicity by influencing the cytoskeleton. New derivatives of the miuraenamides have been synthesized containing a N-methylated amide bond instead of the more easily hydrolysable ester in the natural products. Results: Incorporation of an aromatic side chain onto the C-terminal amino acid of the tripeptide fragment also led to highly active new miuraenamides. Conclusion: We could show that the ester bond of the natural product miuraenamide can be replaced by an N-methyl amide. The yields in the cyclization step are high and generally much better that with the corresponding esters. On the other hand, the biological activity of the new amide analogs are lower compared to the natural products, but the activity can significantly be increased by incorporation of a p-nitrophenyl group at the C-terminus of the peptide fragment.

scholarly journals Plakinamine P, A Steroidal Alkaloid with Bactericidal Activity against Mycobacterium tuberculosis

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 707 ◽  
Author(s):  
Carolina Rodrigues Felix ◽  
Jill C. Roberts ◽  
Priscilla L. Winder ◽  
Rashmi Gupta ◽  
M. Cristina Diaz ◽  
...  
Keyword(s):  
Axial Position ◽  
Side Chain ◽  
Moderate Activity ◽  
Steroidal Alkaloid ◽  
Magnetic Resonance Data ◽  
Resonance Data ◽  
Low Toxicity ◽  
The Common ◽  
Future Work ◽  
Discovery Pipeline

Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus Plakina revealed the presence of a new steroidal alkaloid of the plakinamine class, which we have given the common name plakinamine P. Its structure is most similar to plakinamine L, which also has an acyclic side chain. Careful dissection of the nuclear magnetic resonance data, collected in multiple solvents, suggests that the dimethyl amino group at the 3 position is in an equatorial rather than axial position unlike previously reported plakinamines. Plakinamine P was bactericidal against M. tuberculosis, and exhibited moderate activity against other mycobacterial pathogens, such as M. abscessus and M. avium. Furthermore, it had low toxicity against J774 macrophages, yielding a selectivity index (SI, or IC50/MIC) of 8.4. In conclusion, this work provides a promising scaffold to the tuberculosis drug discovery pipeline. Future work to determine the molecular target of this compound may reveal a pathway essential for M. tuberculosis survival during infection.

scholarly journals Endophytic Actinomycetes: A Novel Source of Potential Acyl Homoserine Lactone Degrading Enzymes

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Surang Chankhamhaengdecha ◽  
Suphatra Hongvijit ◽  
Akkaraphol Srichaisupakit ◽  
Pattra Charnchai ◽  
Watanalai Panbangred
Keyword(s):  
Pathogenic Bacteria ◽  
Sequence Similarity ◽  
Soft Rot ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Amide Bond ◽  
Side Chain ◽  
Signal Molecules ◽  
Endophytic Actinomycetes

Several Gram-negative pathogenic bacteria employN-acyl-L-homoserine lactone (HSL) quorum sensing (QS) system to control their virulence traits. Degradation of acyl-HSL signal molecules by quorum quenching enzyme (QQE) results in a loss of pathogenicity in QS-dependent organisms. The QQE activity of actinomycetes in rhizospheric soil and inside plant tissue was explored in order to obtain novel strains with high HSL-degrading activity. Among 344 rhizospheric and 132 endophytic isolates, 127 (36.9%) and 68 (51.5%) of them, respectively, possessed the QQE activity. The highest HSL-degrading activity was at151.30±3.1 nmole/h/mL from an endophytic actinomycetes isolate, LPC029. The isolate was identified asStreptomycesbased on16S  rRNAgene sequence similarity. The QQE from LPC029 revealed HSL-acylase activity that was able to cleave an amide bond of acyl-side chain in HSL substrate as determined by HPLC. LPC029 HSL-acylase showed broad substrate specificity from C6- to C12-HSL in which C10HSL is the most favorable substrate for this enzyme. In anin vitropathogenicity assay, the partially purified HSL-acylase efficiently suppressed soft rot of potato caused byPectobacterium carotovorumssp.carotovorumas demonstrated. To our knowledge, this is the first report of HSL-acylase activity derived from an endophyticStreptomyces.

scholarly journals Microbiological degradation of bile acids. Nitrogenous hexahydroindane derivatives formed from cholic acid by Streptomyces rubescens

1976 ◽  
Vol 160 (3) ◽  
pp. 745-755 ◽  
Author(s):  
S Hayakawa ◽  
S Hashimoto ◽  
T Onaka
Keyword(s):  
Cholic Acid ◽  
Bond Formation ◽  
Valeric Acid ◽  
Amide Bond ◽  
Side Chain ◽  
Mechanism Of Formation ◽  
Partial Synthesis ◽  
Degradative Pathway ◽  
Amide Bond Formation ◽  
New Compounds

The metabolism of cholic acid (I) by Streptomyces rubescens was investigated. This organism effected ring A cleavage, side-chain shortening and amide bond formation and gave the following metabolites: (4R)-4-[4α-(2-carboxyethyl)-3aα-hexahydro-7aβ-methyl-5-oxoindan-1 β-yl]valeric acid (IIa) and its mono-amide (valeramide) (IIb); and 2,3,4,6, 6aβ,7,8,9,9aα,9bβ-decahydro-6aβ-methyl-1H-cyclopenta[f]quinoline-3,7-dione(IIIe)and its homologues with the β-oriented side chains, valeric acid, valeramide, butanone and propionic acid, in the place of the oxo group at C-7, i.e.compounds (IIIa), (IIIb), (IIIc) and (IIId) respectively. All the nitrogenous metabolites were new compounds, and their structures were established by partial synthesis except for the metabolite (IIIc). The mechanism of formation of these metabolites is considered. A degradative pathway of cholic acid (I) into the metabolites is also tentatively proposed.

scholarly journals Chemical nature and sequence of alamethicin

1976 ◽  
Vol 153 (2) ◽  
pp. 181-190 ◽  
Author(s):  
D R Martin ◽  
R J P Williams
Keyword(s):  
Glutamic Acid ◽  
Chemical Nature ◽  
Chemical Compounds ◽  
Amide Bond ◽  
Side Chain ◽  
Partial Hydrolysis ◽  
Spectroscopy Study ◽  
N Terminus ◽  
Acetyl Group ◽  
New Formula

An n.m.r. spectroscopy study of pure alamethicin shows it to be a linear polypeptide of 19 residues. The N-terminus is blocked by an acetyl group, and the eighteenth residue, glutamic acid, is linked by an amide bond on its side chain to phenylalaninol (Fig. 6). The new formula is confirmed by a comparison between pure chemical compounds and the products of partial hydrolysis.

scholarly journals Sterol Side Chain Reductase 2 Is a Key Enzyme in the Biosynthesis of Cholesterol, the Common Precursor of Toxic Steroidal Glycoalkaloids in Potato

2014 ◽  
Vol 26 (9) ◽  
pp. 3763-3774 ◽  
Author(s):  
S. Sawai ◽  
K. Ohyama ◽  
S. Yasumoto ◽  
H. Seki ◽  
T. Sakuma ◽  
...  
Keyword(s):  
Side Chain ◽  
Common Precursor ◽  
Key Enzyme ◽  
The Common

Effect of hydroxamic acids on growth and urease activity in Corynebacterium renale

1976 ◽  
Vol 22 (4) ◽  
pp. 544-551 ◽  
Author(s):  
Robert M. Nervig ◽  
Solomon Kadis
Keyword(s):  
Urease Activity ◽  
Hydroxamic Acids ◽  
Terminal Group ◽  
Side Chain ◽  
Acetohydroxamic Acid ◽  
Maximal Growth ◽  
Maximal Inhibition ◽  
Intact Cells ◽  
Lag Period ◽  
The Common

Studies were conducted on the effect of four different hydroxamic acids (HA), hydroxyurea, acetohydroxamic acid, p-fluorobenzoylhydroxamic acid and sorbylhydroxamic acid, on the growth and urease activity of Corynebacterium renale. The addition of each of these HA, at concentrations ranging from 10−3 to 10−5 M, to medium containing urea as the sole nitrogen source resulted in a lengthened lag period of growth the extent of which depended upon the concentration of each HA tested as well as the structure of the compound; that is, the size and (or) complexity of the side chain attached to the common terminal group of the molecule. However, the maximal growth levels achieved following conclusion of the exponential phase were not affected by the HA. Investigations on the effect of these HA on the urease activity of intact cells as well as cell-free extracts revealed that in each case the enzymatic activity was inhibited by each of the HA tested. The extent of inhibition with the intact cells was about one-half of that observed with cell-free extracts. Direct incubation of cell-free extracts as well as intact cells with each of the HA tested was required for maximal inhibition.

scholarly journals The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

2015 ◽  
Vol 11 ◽  
pp. 2029-2037 ◽  
Author(s):  
Christine Cychon ◽  
Ellen Lichte ◽  
Matthias Köck
Keyword(s):  
Marine Sponge ◽  
Major Metabolite ◽  
Chemical Investigation ◽  
Amide Bond ◽  
Methyl Derivative ◽  
Pyridinium Ring ◽  
Ester Linkage ◽  
The Common ◽  
The Caribbean ◽  
Derivatives Of

The chemical investigation of the Caribbean sponge Agelas citrina revealed four new pyrrole–imidazole alkaloids (PIAs), the citrinamines A–D (1–4) and the bromopyrrole alkaloid N-methylagelongine (5). All citrinamines are dimers of hymenidin (6) which was also isolated from this sponge as the major metabolite. Citrinamines A (1) and B (2) are derivatives of the PIA dimer mauritiamine (7), whereas citrinamine C (3) is derived from the PIA dimer nagelamide B (8). Citrinamine D (4) shows an uncommon linkage between the imidazole rings of both monomeric units as it is only observed in the benzocyclobutane ring moiety of benzosceptrins A–C (9–11). Compound 5 is the N-methyl derivative of agelongine (12) which consist of a pyridinium ring and an ester linkage instead of the aminoimidazole moiety and the common amide bond in PIAs.

Synthesis and Mesophse Study on a Triphenylene-Based Polysiloxane

2011 ◽  
Vol 181-182 ◽  
pp. 139-142
Author(s):  
Chun Xiu Zhang ◽  
Jia Ling Pu ◽  
Hao Wu ◽  
Ao Zhang ◽  
Ming Xia Zhang ◽  
...  
Keyword(s):  
Differential Scanning Calorimeter ◽  
Allyl Bromide ◽  
Optical Microscope ◽  
Side Chain ◽  
The Common

A side chain triphenylene-based polysiloxane were synthesized from 2-hydroxy-3-Methoxy-6,7,10,11–tetrapentyloxy-triphenylene.2-hydroxy-3-Methoxy-6,7,10,11–tetrapentyloxy triphenylene was synthesized via the common synthisis route including the Williamson Etherification of catechol, the iodination of 1,2-dipentyloxybenzene, the Ullman Coupling and the coupling of 3,3'-4,4'–tetrapentyloxy diphenyl and methoxy-phenol; 2-allyloxyl-3-Methoxy-6, 7, 10, 11–tetrapentyloxytriphenylene was synthesized by the etherification of 2-hydroxy-3-Methoxy-6,7,10, 11–tetrapentyloxytriphenylene and allyl bromide; the polysiloxane was synthesized by addition of 2-allyloxyl-3-Methoxy-6,7,10,11–tetrapentyloxytriphenylene and polydimethylsiloxane. The structures of the compounds were determined by FTIR and 1HNMR. Mesophase and their structural orders were determined using a polarized optical microscope and a differential scanning calorimeter.

Sign in / Sign up

Export Citation Format

Share Document