20 research outputs found
Формування органів управління кінематографа в Україні (1919)
У статті розглядається процес створення та діяльність органів управління кінематографа в перші роки функціонування радянської влади в Україні.В статье рассматривается процесс создания и деятельность органов управления кинематографа в первые годы функционирования советской власти в Украине.The process of creating and functioning of the cinematography authorities in the early years of the Soviet Union in Ukraine is examined in the article
Efficient reagent-saving method for the N-terminal labeling of bioactive peptides with organometallic carboxylic acids by solid-phase synthesis
Labeling of biomolecules with organometallic moieties holds great promise as a tool for chemical biology and for the investigation of biochemical signaling pathways. Herein, we report a robust and reproducible synthetic strategy for the synthesis of ruthenocenecarboxylic acid, giving the acid in 53% overall yield. This organometallic label was conjugated via solid-phase peptide synthesis in near-quantitative yield to a number of different biologically active peptides, using only 1 equiv of the acid and coupling reagents, thereby avoiding wasting the precious organometallic acid. This optimized method of stoichiometric N-terminal acylation was then also successfully applied to conjugating ferrocenecarboxylic acid and a novel organometallic ReI(CO)3 complex, showing the generality of the synthetic procedure
A sustainable approach to inward investment?
Also known as Insights publication seriesAvailable from British Library Document Supply Centre-DSC:4024.086045(3) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Efficient Reagent-Saving Method for the N‑Terminal Labeling of Bioactive Peptides with Organometallic Carboxylic Acids by Solid-Phase Synthesis
Labeling
of biomolecules with organometallic moieties holds great
promise as a tool for chemical biology and for the investigation of
biochemical signaling pathways. Herein, we report a robust and reproducible
synthetic strategy for the synthesis of ruthenocenecarboxylic acid,
giving the acid in 53% overall yield. This organometallic label was
conjugated via solid-phase peptide synthesis in near-quantitative
yield to a number of different biologically active peptides, using
only 1 equiv of the acid and coupling reagents, thereby avoiding wasting
the precious organometallic acid. This optimized method of stoichiometric
N-terminal acylation was then also successfully applied to conjugating
ferrocenecarboxylic acid and a novel organometallic Re<sup>I</sup>(CO)<sub>3</sub> complex, showing the generality of the synthetic
procedure
Efficient Reagent-Saving Method for the N‑Terminal Labeling of Bioactive Peptides with Organometallic Carboxylic Acids by Solid-Phase Synthesis
Labeling
of biomolecules with organometallic moieties holds great
promise as a tool for chemical biology and for the investigation of
biochemical signaling pathways. Herein, we report a robust and reproducible
synthetic strategy for the synthesis of ruthenocenecarboxylic acid,
giving the acid in 53% overall yield. This organometallic label was
conjugated via solid-phase peptide synthesis in near-quantitative
yield to a number of different biologically active peptides, using
only 1 equiv of the acid and coupling reagents, thereby avoiding wasting
the precious organometallic acid. This optimized method of stoichiometric
N-terminal acylation was then also successfully applied to conjugating
ferrocenecarboxylic acid and a novel organometallic Re<sup>I</sup>(CO)<sub>3</sub> complex, showing the generality of the synthetic
procedure
Synthese en toepassing van een lipofiel aminozuurderivaat voor het verbeteren van de membraanaffiniteit van antimicrobiële peptiden
OBJECTIVE: To increase the potential of membrane-acting peptides as possible novel drug-like compounds by increasing lipophilicity and thereby enhancing membrane affinity. DESIGN: An Fmoc-protected enantiomerically pure lipophilic amino acid (Fmoc-Lad-OH), which contains a nine carbon atom hydrophobic side chain, was designed. Fmoc-Lad-OH can be introduced into any peptide sequence using standard solid phase peptide synthesis to increase the lipophilicity of a peptide without sacrificing important polar segments of a peptide like for instance the N and C-termini. The antimicrobial decapeptide anoplin was chosen as a model peptide to test the hypothesis. METHODS: Fmoc-Lad-OH was prepared via organic synthesis and incorporated into the anoplin peptide sequence using solid-phase peptide synthesis followed by reversed-phase HPLC purification. Biological activity was evaluated using microtiter dilution bacterial growth assays, haemolytic assays and membrane vesicle leakage experiments. RESULTS: All three lipophilic analogues show a dramatic increase in antimicrobial activity: up to 4-8 times better for Escherichia coli (Gram-negative] and over one order of magnitude for Staphylococcus aureus (Gram-positive) compared to anoplin. Although the haemolytic activity was increased for the lipophilic analogues, the concentration at which 50% lysis will occur (EC50) was still one order of magnitude higher than the determined MICs. In the membrane vesicle leakage experiments the lipophilic analogues showed a higher lytic activity than anoplin, in agreement with the observed MIC values. CONCLUSION: Introduction of Lad into anoplin clearly showed a positive effect, which suggests that Fmoc-Lad-OH could be used as a general approach to increase membrane affinity of membrane-acting peptides
Synthese en toepassing van een lipofiel aminozuurderivaat voor het verbeteren van de membraanaffiniteit van antimicrobiële peptiden
OBJECTIVE: To increase the potential of membrane-acting peptides as possible novel drug-like compounds by increasing lipophilicity and thereby enhancing membrane affinity. DESIGN: An Fmoc-protected enantiomerically pure lipophilic amino acid (Fmoc-Lad-OH), which contains a nine carbon atom hydrophobic side chain, was designed. Fmoc-Lad-OH can be introduced into any peptide sequence using standard solid phase peptide synthesis to increase the lipophilicity of a peptide without sacrificing important polar segments of a peptide like for instance the N and C-termini. The antimicrobial decapeptide anoplin was chosen as a model peptide to test the hypothesis. METHODS: Fmoc-Lad-OH was prepared via organic synthesis and incorporated into the anoplin peptide sequence using solid-phase peptide synthesis followed by reversed-phase HPLC purification. Biological activity was evaluated using microtiter dilution bacterial growth assays, haemolytic assays and membrane vesicle leakage experiments. RESULTS: All three lipophilic analogues show a dramatic increase in antimicrobial activity: up to 4-8 times better for Escherichia coli (Gram-negative] and over one order of magnitude for Staphylococcus aureus (Gram-positive) compared to anoplin. Although the haemolytic activity was increased for the lipophilic analogues, the concentration at which 50% lysis will occur (EC50) was still one order of magnitude higher than the determined MICs. In the membrane vesicle leakage experiments the lipophilic analogues showed a higher lytic activity than anoplin, in agreement with the observed MIC values. CONCLUSION: Introduction of Lad into anoplin clearly showed a positive effect, which suggests that Fmoc-Lad-OH could be used as a general approach to increase membrane affinity of membrane-acting peptides
Synthesis, antimicrobial activity, and membrane permeabilizing properties of C-terminally modified nisin conjugates accessed by CuAAC
Functionalization of the lantibiotic nisin with fluorescent reporter molecules is highly important for the understanding of its mode of action as a potent antimicrobial peptide. In addition to this, multimerization of nisin to obtain multivalent peptide constructs and conjugation of nisin to bioactive molecules or grafting it on surfaces can be attractive methods for interference with bacterial growth. Here, we report a convenient method for the synthesis of such nisin conjugates and show that these nisin derivatives retain both their antimicrobial activity and their membrane permeabilizing properties. The synthesis is based on the Cu(I)-catalyzed alkyne–azide cycloaddition reaction (CuAAC) as a bioorthogonal ligation method for large and unprotected peptides in which nisin was C-terminally modified with propargylamine and subsequently efficiently conjugated to a series of functionalized azides. Two fluorescently labeled nisin conjugates together with a dimeric nisin construct were prepared while membrane insertion as well as antimicrobial activity were unaffected by these modifications. This study shows that C-terminal modification of nisin does not deteriorate biological activity in sharp contrast to N-terminal modification and therefore C-terminally modified nisin analogues are valuable tools to study the antibacterial mode of action of nisin. Furthermore, the ability to use stoichiometric amounts of the azide containing molecule opens up possibilities for surface tethering and more complex multivalent structures
Synthesis of nisin AB dicarba analogs using ring-closing metathesis: Influence of sp<sup>3</sup>versus sp<sup>2</sup> hybridization of the α-carbon atom of residues dehydrobutyrine-2 and dehydroalanine-5 on the lipid II binding affinity
Herein the synthesis of two nisin AB dicarba analogs is described, focusing on amino acid modifications at positions 2 and 5. The nisin mimics were synthesized by a combination of solid phase synthesis of the linear peptides, followed by macrocyclization via ring-closing metathesis and fragment assembly by means of solution phase chemistry. The two N-terminal nisin AB-fragment mimics contain either the native dehydrobutyrine (Dhb)/dehydroalanine (Dha) amino acid residues or alanine at position 2 and 5, respectively. The native dehydrobutyrine at position 2 and dehydroalanine at position 5 were introduced as their precursors, namely threonine and serine, respectively, and subsequent dehydration was carried out by EDCI/CuCl as the condensing agent. Both AB-fragment mimics were analyzed in a lipid II binding assay and it was found that the Ala2/Ala5 AB-mimic (2) showed a reduced activity, while the Dhb2/Dha5 AB-mimic (3) was as active as the native AB-fragment (1)
Synthesis, Antimicrobial Activity, and Membrane Permeabilizing Properties of C‑Terminally Modified Nisin Conjugates Accessed by CuAAC
Functionalization of the lantibiotic
nisin with fluorescent reporter
molecules is highly important for the understanding of its mode of
action as a potent antimicrobial peptide. In addition to this, multimerization
of nisin to obtain multivalent peptide constructs and conjugation
of nisin to bioactive molecules or grafting it on surfaces can be
attractive methods for interference with bacterial growth. Here, we
report a convenient method for the synthesis of such nisin conjugates
and show that these nisin derivatives retain both their antimicrobial
activity and their membrane permeabilizing properties. The synthesis
is based on the Cu(I)-catalyzed alkyne–azide cycloaddition
reaction (CuAAC) as a bioorthogonal ligation method for large and
unprotected peptides in which nisin was C-terminally modified with
propargylamine and subsequently efficiently conjugated to a series
of functionalized azides. Two fluorescently labeled nisin conjugates
together with a dimeric nisin construct were prepared while membrane
insertion as well as antimicrobial activity were unaffected by these
modifications. This study shows that C-terminal modification of nisin
does not deteriorate biological activity in sharp contrast to N-terminal
modification and therefore C-terminally modified nisin analogues are
valuable tools to study the antibacterial mode of action of nisin.
Furthermore, the ability to use stoichiometric amounts of the azide
containing molecule opens up possibilities for surface tethering and
more complex multivalent structures