scholarly journals Modulation of cytochrome c spin states by lipid acyl chains: a continuous-wave electron paramagnetic resonance (CW-EPR) study of haem iron

2003 ◽  
Vol 370 (2) ◽  
pp. 671-678 ◽  
Author(s):  
Maria R. ZUCCHI ◽  
Otaciro R. NASCIMENTO ◽  
Adelaide FALJONI-ALARIO ◽  
Tatiana PRIETO ◽  
Iseli L. NANTES
Keyword(s):  
Cytochrome C ◽  
Spin State ◽  
Continuous Wave ◽  
Acyl Chain ◽  
Clear Correlation ◽  
Head Group ◽  
Spin States ◽  
Protein Ratio ◽  
Unsaturated Lipids ◽  
Rhombic Symmetry

This work is a systematic study, showing a clear correlation between the nature of the lipid acyl chain and the spin states of cytochrome c interacting with different types of lipid membranes. According to the lipid acyl chain type, and the head group charge present in the bilayer, three spin states of cytochrome c were observed in different proportions: the native cytochrome c low spin state with rhombic symmetry (spin 1/2, g//=3.07 and g⊥=2.23), a low spin state with less rhombic symmetry (spin 1/2, g1 = 2.902, g2 = 2.225, and g3 = 1.510) and the high spin state (spin 5/2, g// = 6.0 and g⊥ = 2.0). The proportion of the spin states of cytochrome c bound to bilayers was also dependent on the lipid/protein ratio, suggesting the existence of two or more protein sites interacting with the lipids. The lipid-induced alterations in the symmetry and spin states of cytochrome c exhibited partial reversibility when the ionic strength was increased, which reinforces the crucial role played by the electrostatic interaction with the lipid bilayer. Different cytochrome c spin states exhibited corresponding modifications in the haemprotein UV/visible spectra, particularly in the Q-band associated with loss of the 695nm band and appearance of a band in the region of 600—650nm. The observed reactivity of cytochrome c with oxidized forms of unsaturated lipids reinforces the possibility of the acyl chain insertion in the haemprotein structure.

Mechanisms of Drug Solubilization by Polar Lipids in Biorelevant Media

2020 ◽  
Author(s):  
Vladimir Katev ◽  
Zahari Vinarov ◽  
Slavka S. Tcholakova
Keyword(s):  
Chain Length ◽  
Acyl Chain ◽  
Polar Lipids ◽  
Superior Performance ◽  
Head Group ◽  
Formulation Development ◽  
Biorelevant Media ◽  
Drug Solubilization ◽  
Colloidal Aggregates ◽  
Class 1

Despite the widespread use of lipid excipients in both academic research and oral formulation development, rational selection guidelines are still missing. In the current study, we aimed to establish a link between the molecular structure of commonly used polar lipids and drug solubilization in biorelevant media. We studied the effect of 26 polar lipids of the fatty acid, phospholipid or monoglyceride type on the solubilization of fenofibrate in a two-stage <i>in vitro</i> GI tract model. The main trends were checked also with progesterone and danazol.<br>Based on their fenofibrate solubilization efficiency, the polar lipids can be grouped in 3 main classes. Class 1 substances (n = 5) provide biggest enhancement of drug solubilization (>10-fold) and are composed only by unsaturated compounds. Class 2 materials (n = 10) have an intermediate effect (3-10 fold increase) and are composed primarily (80 %) of saturated compounds. Class 3 materials (n = 11) have very low or no effect on drug solubilization and are entirely composed of saturated compounds.<br>The observed behaviour of the polar lipids was rationalized by using two classical physicochemical parameters: the acyl chain phase transition temperature (<i>T</i><sub>m</sub>) and the critical micellar concentration (CMC). Hence, the superior performance of class 1 polar lipids was explained by the double bonds in their acyl chains, which: (1) significantly decrease <i>T</i><sub>m</sub>, allowing these C18 lipids to form colloidal aggregates and (2) prevent tight packing of the molecules in the aggregates, resulting in bigger volume available for drug solubilization. Long-chain (C18) saturated polar lipids had no significant effect on drug solubilization because their <i>T</i><sub>m</sub> was much higher than the temperature of the experiment (<i>T</i> = 37 C) and, therefore, their association in colloidal aggregates was limited. On the other end of the spectrum, the short chain octanoic acid manifested a high CMC (50 mM), which had to be exceeded in order to enhance drug solubilization. When these two parameters were satisfied (C > CMC, <i>T</i><sub>m</sub> < <i>T</i><sub>exp</sub>), the increase of the polar lipid chain length increased the drug solubilization capacity (similarly to classical surfactants), due to the decreased CMC and bigger volume available for solubilization.<br>The hydrophilic head group also has a dramatic impact on the drug solubilization enhancement, with polar lipids performance decreasing in the order: choline phospholipids > monoglycerides > fatty acids.<br>As both the acyl chain length and the head group type are structural features of the polar lipids, and not of the solubilized drugs, the impact of <i>T</i><sub>m</sub> and CMC on solubilization by polar lipids should hold true for a wide variety of hydrophobic molecules. The obtained mechanistic insights can guide rational drug formulation development and thus support modern drug discovery pipelines.<br>

Mechanisms of Drug Solubilization by Polar Lipids in Biorelevant Media

2020 ◽  
Author(s):  
Vladimir Katev ◽  
Zahari Vinarov ◽  
Slavka S. Tcholakova
Keyword(s):  
Chain Length ◽  
Acyl Chain ◽  
Polar Lipids ◽  
Superior Performance ◽  
Head Group ◽  
Formulation Development ◽  
Biorelevant Media ◽  
Drug Solubilization ◽  
Colloidal Aggregates ◽  
Class 1

Despite the widespread use of lipid excipients in both academic research and oral formulation development, rational selection guidelines are still missing. In the current study, we aimed to establish a link between the molecular structure of commonly used polar lipids and drug solubilization in biorelevant media. We studied the effect of 26 polar lipids of the fatty acid, phospholipid or monoglyceride type on the solubilization of fenofibrate in a two-stage <i>in vitro</i> GI tract model. The main trends were checked also with progesterone and danazol.<br>Based on their fenofibrate solubilization efficiency, the polar lipids can be grouped in 3 main classes. Class 1 substances (n = 5) provide biggest enhancement of drug solubilization (>10-fold) and are composed only by unsaturated compounds. Class 2 materials (n = 10) have an intermediate effect (3-10 fold increase) and are composed primarily (80 %) of saturated compounds. Class 3 materials (n = 11) have very low or no effect on drug solubilization and are entirely composed of saturated compounds.<br>The observed behaviour of the polar lipids was rationalized by using two classical physicochemical parameters: the acyl chain phase transition temperature (<i>T</i><sub>m</sub>) and the critical micellar concentration (CMC). Hence, the superior performance of class 1 polar lipids was explained by the double bonds in their acyl chains, which: (1) significantly decrease <i>T</i><sub>m</sub>, allowing these C18 lipids to form colloidal aggregates and (2) prevent tight packing of the molecules in the aggregates, resulting in bigger volume available for drug solubilization. Long-chain (C18) saturated polar lipids had no significant effect on drug solubilization because their <i>T</i><sub>m</sub> was much higher than the temperature of the experiment (<i>T</i> = 37 C) and, therefore, their association in colloidal aggregates was limited. On the other end of the spectrum, the short chain octanoic acid manifested a high CMC (50 mM), which had to be exceeded in order to enhance drug solubilization. When these two parameters were satisfied (C > CMC, <i>T</i><sub>m</sub> < <i>T</i><sub>exp</sub>), the increase of the polar lipid chain length increased the drug solubilization capacity (similarly to classical surfactants), due to the decreased CMC and bigger volume available for solubilization.<br>The hydrophilic head group also has a dramatic impact on the drug solubilization enhancement, with polar lipids performance decreasing in the order: choline phospholipids > monoglycerides > fatty acids.<br>As both the acyl chain length and the head group type are structural features of the polar lipids, and not of the solubilized drugs, the impact of <i>T</i><sub>m</sub> and CMC on solubilization by polar lipids should hold true for a wide variety of hydrophobic molecules. The obtained mechanistic insights can guide rational drug formulation development and thus support modern drug discovery pipelines.<br>

scholarly journals Carboxylic Ester Hydrolases in Bacteria: Active Site, Structure, Function and Application

Crystals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 597 ◽  
Author(s):  
Changsuk Oh ◽  
T. Doohun Kim ◽  
Kyeong Kyu Kim
Keyword(s):  
Acyl Chain ◽  
Data Bank ◽  
Industrial Applications ◽  
Head Group ◽  
Carboxylic Ester ◽  
Site Structure ◽  
Domains Of Life ◽  
Carboxylic Esters ◽  
Hydrolysis Of ◽  
Ester Hydrolases

Carboxylic ester hydrolases (CEHs), which catalyze the hydrolysis of carboxylic esters to produce alcohol and acid, are identified in three domains of life. In the Protein Data Bank (PDB), 136 crystal structures of bacterial CEHs (424 PDB codes) from 52 genera and metagenome have been reported. In this review, we categorize these structures based on catalytic machinery, structure and substrate specificity to provide a comprehensive understanding of the bacterial CEHs. CEHs use Ser, Asp or water as a nucleophile to drive diverse catalytic machinery. The α/β/α sandwich architecture is most frequently found in CEHs, but 3-solenoid, β-barrel, up-down bundle, α/β/β/α 4-layer sandwich, 6 or 7 propeller and α/β barrel architectures are also found in these CEHs. Most are substrate-specific to various esters with types of head group and lengths of the acyl chain, but some CEHs exhibit peptidase or lactamase activities. CEHs are widely used in industrial applications, and are the objects of research in structure- or mutation-based protein engineering. Structural studies of CEHs are still necessary for understanding their biological roles, identifying their structure-based functions and structure-based engineering and their potential industrial applications.

Interactions of the Antimicrobial Peptide Maculatin 1.1 and Analogues with Phospholipid Bilayers

2011 ◽  
Vol 64 (6) ◽  
pp. 798 ◽  
Author(s):  
David I. Fernandez ◽  
Marc-Antoine Sani ◽  
Frances Separovic
Keyword(s):  
Antimicrobial Peptide ◽  
Solid State Nmr ◽  
Acyl Chain ◽  
Head Group ◽  
Group Interactions ◽  
Bacterial Membranes ◽  
Helical Content ◽  
Lipid System ◽  
Acyl Chains ◽  
Mixed Bilayer

The interactions of the antimicrobial peptide, maculatin 1.1 (GLFGVLAKVAAHVVPAIAEHF-NH2) and two analogues, with model phospholipid membranes have been studied using solid-state NMR and circular dichroism spectroscopy. Maculatin 1.1 and the P15G and P15A analogues displayed minimal secondary structure in water, but with zwitterionic dimyristoylphosphatidylcholine (DMPC) vesicles displayed a significant increase in α-helical content. In mixed phospholipid vesicles of DMPC and anionic dimyristoylphosphatidylglycerol (DMPG), each peptide was highly structured with ~80% α-helical content. In DMPC vesicles, the native peptide displayed moderate head group interaction and significant perturbation of the lipid acyl chains. In DMPC/DMPG vesicles, maculatin 1.1 promoted formation of a DMPG-enriched phase and moderately increased disorder towards acyl chain ends of DMPC in the mixed bilayer. Both analogues showed reduced phospholipid head group interactions with DMPC but displayed significant interactions with the mixed lipid system. These effects support the preferential activity of these antimicrobial peptides for bacterial membranes.

scholarly journals Structural Characterization of Natural Yeast Phosphatidylcholine and Bacterial Phosphatidylglycerol Lipid Multilayers by Neutron Diffraction

2021 ◽  
Vol 9 ◽  
Author(s):  
Alessandra Luchini ◽  
Giacomo Corucci ◽  
Krishna Chaithanya Batchu ◽  
Valerie Laux ◽  
Michael Haertlein ◽  
...  
Keyword(s):  
Neutron Diffraction ◽  
Acyl Chain ◽  
Model Systems ◽  
Head Group ◽  
Single Class ◽  
Lipid Mixtures ◽  
Chain Composition ◽  
Acyl Chain Composition ◽  
The Impact

Eukaryotic and prokaryotic cell membranes are difficult to characterize directly with biophysical methods. Membrane model systems, that include fewer molecular species, are therefore often used to reproduce their fundamental chemical and physical properties. In this context, natural lipid mixtures directly extracted from cells are a valuable resource to produce advanced models of biological membranes for biophysical investigations and for the development of drug testing platforms. In this study we focused on single phospholipid classes, i.e. Pichia pastoris phosphatidylcholine (PC) and Escherichia coli phosphatidylglycerol (PG) lipids. These lipids were characterized by a different distribution of their respective acyl chain lengths and number of unsaturations. We produced both hydrogenous and deuterated lipid mixtures. Neutron diffraction experiments at different relative humidities were performed to characterize multilayers from these lipids and investigate the impact of the acyl chain composition on the structural organization. The novelty of this work resides in the use of natural extracts with a single class head-group and a mixture of chain compositions coming from yeast or bacterial cells. The characterization of the PC and PG multilayers showed that, as a consequence of the heterogeneity of their acyl chain composition, different lamellar phases are formed.

scholarly journals Manipulating metal spin states for biomimetic, catalytic and molecular materials chemistry

2020 ◽  
Vol 49 (44) ◽  
pp. 15560-15567 ◽  
Author(s):  
Malcolm A. Halcrow
Keyword(s):  
Base Metal ◽  
Spin State ◽  
Light Harvesting ◽  
Ligand Design ◽  
Spin States ◽  
Materials Chemistry ◽  
Molecular Materials ◽  
Metal Compounds ◽  
The Relationship

The relationship between ligand design and spin state in base metal compounds is surveyed. Implications and applications of these principles for light-harvesting dyes, catalysis and materials chemistry are summarised.

Paramagnetic properties of the low- and high-spin states of yeast cytochrome c peroxidase

2013 ◽  
Vol 57 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Sophie Vanwetswinkel ◽  
Nico A. J. van Nuland ◽  
Alexander N. Volkov
Keyword(s):  
Cytochrome C ◽  
High Spin ◽  
Cytochrome C Peroxidase ◽  
Spin States ◽  
High Spin States ◽  
Paramagnetic Properties

scholarly journals Acyl Chain and Head Group Regulation of Phospholipid Catabolism in Senescing Carnation Flowers

1991 ◽  
Vol 95 (3) ◽  
pp. 909-916 ◽  
Author(s):  
Jacqueline H. Brown ◽  
James A. Chambers ◽  
John E. Thompson
Keyword(s):  
Acyl Chain ◽  
Head Group
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