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

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.

Investigations of Interactions Between Altretamine and Model Membranes: Spectroscopic and Calorimetric Analysis

2019 ◽  
Vol 14 (04) ◽  
pp. 197-215
Author(s):  
D. Bilge ◽  
N. Civelek ◽  
Z. Özçelik Çetinel
Keyword(s):  
Molecular Level ◽  
Acyl Chain ◽  
Spectroscopic Studies ◽  
Model Membranes ◽  
Head Group ◽  
Scanning Calorimetry ◽  
Calorimetric Analysis ◽  
Multilamellar Vesicles ◽  
Calorimetric Studies ◽  
Chain Lengths

Altretamine (ALT) is a Food and Drug Administration (FDA) approved antineoplastic drug particularly used for ovarian cancer. This study examined, at a molecular level, the interactions of the drug with model membranes composed of phospholipids with different acyl chain lengths and head group charges at varied ALT concentrations based on temperature. For this purpose, spectroscopic studies of the liposomes in multilamellar vesicles form were conducted by Fourier transform-infrared spectroscopy (FTIR) and their calorimetric studies were carried out by differential scanning calorimetry (DSC) techniques. The results of the study showed that ALT clearly interacted with lipids and that these interactions were more significant in multilamellar vesicles made up of short chain phospholipids. Moreover, the results suggested that ALT settled into the tail group region, in particular the region that formed the hydrophobic part of lipids, and this effects the whole section of the membranes including glycerol backbones and head groups. This study is expected to contribute, on molecular level, to the studies on the knowledge of the mechanism in cancer, which is still very much a dangerous disease, and its related treatment.

scholarly journals Endocytic Sorting of Lipid Analogues Differing Solely in the Chemistry of Their Hydrophobic Tails

1999 ◽  
Vol 144 (6) ◽  
pp. 1271-1284 ◽  
Author(s):  
Sushmita Mukherjee ◽  
Thwe Thwe Soe ◽  
Frederick R. Maxfield
Keyword(s):  
Acyl Chain ◽  
Tail Length ◽  
Head Group ◽  
Membrane Domains ◽  
Endocytic Recycling ◽  
Late Endosomes ◽  
Endocytic Sorting ◽  
Membrane Components ◽  
Quantitative Fluorescence ◽  
Alkyl Tail

To understand the mechanisms for endocytic sorting of lipids, we investigated the trafficking of three lipid-mimetic dialkylindocarbocyanine (DiI) derivatives, DiIC16(3) (1,1′-dihexadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate), DiIC12(3) (1,1′- didodecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate), and FAST DiI (1,1′-dilinoleyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate), in CHO cells by quantitative fluorescence microscopy. All three DiIs have the same head group, but differ in their alkyl tail length or unsaturation; these differences are expected to affect their distribution in membrane domains of varying fluidity or curvature. All three DiIs initially enter sorting endosomes containing endocytosed transferrin. DiIC16(3), with two long 16-carbon saturated tails is then delivered to late endosomes, whereas FAST DiI, with two cis double bonds in each tail, and DiIC12(3), with saturated but shorter (12-carbon) tails, are mainly found in the endocytic recycling compartment. We also find that DiOC16(3) (3,3′- dihexadecyloxacarbocyanine perchlorate) and FAST DiO (3,3′-dilinoleyloxacarbocyanine perchlorate) behave similarly to their DiI counterparts. Furthermore, whereas a phosphatidylcholine analogue with a BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophore attached at the end of a 5-carbon acyl chain is delivered efficiently to the endocytic recycling compartment, a significant fraction of another derivative with BODIPY attached to a 12-carbon acyl chain entered late endosomes. Our results thus suggest that endocytic organelles can sort membrane components efficiently based on their preference for association with domains of varying characteristics.

scholarly journals Differential hepatic processing and biliary secretion of head-group and acyl chains of liposomal phosphatidylcholines

1991 ◽  
Vol 275 (1) ◽  
pp. 139-144 ◽  
Author(s):  
H J Verkade ◽  
J T Derksen ◽  
A Gerding ◽  
G L Scherphof ◽  
R J Vonk ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Degradation Products ◽  
Acyl Chain ◽  
Quantitative Difference ◽  
Biliary Secretion ◽  
Synthesis Rate ◽  
Head Group ◽  
Bile Drainage ◽  
Acyl Chains

To investigate the contribution of plasma-derived phosphatidylcholine (PC) to bile PC, the hepatic processing and biliary secretion of liposome-associated PC was studied in rats. For this purpose, small unilamellar vesicles (SUV), containing trace amounts of [2-palmitoyl-9,10-3H]dipalmitoylphosphatidylcholine ([palmitoyl-3H]DPPC), [choline-14C]-dipalmitoylphosphatidylcholine ([choline-14C]DPPC), di[14C]palmitoylphosphatidylcholine ([14C]DPPC) or di[1-14C]-oleoylphosphatidylcholine ([14C]DOPC), were administered intravenously to unanaesthetized rats, equipped with permanent catheters in heart and bile duct. Biliary secretion of the 14C-head-group label of DPPC was very slow (0.3% of injected dose in 4 h), whereas the [3H]palmitoyl label was secreted at a much higher rate (16% in 4 h), but only after substantial catabolism of the acyl chain. To study the latter process in more detail, we compared hepatic metabolism and biliary secretion of [1-14C]acyl-labelled DPPC and DOPC. In rats with an 8-day bile drainage, degradation products of the oleoyl chain were utilized for synthesis of bile acids, which were subsequently secreted into the bile (2% in 6 h). A much smaller fraction (0.6% in 6 h) was secreted as PC and lyso-PC. When bile drainage was started immediately after SUV injection, i.e. a situation with a low hepatic bile acid synthesis rate and a high phospholipid secretion, the secretion of [14C]DOPC-derived radioactivity in the form of bile acids was decreased (0.2% in 6 h), and that as (lyso-)PC increased (1.5% in 6 h). Biliary secretion of DPPC palmitoyl chains in bile-diverted rats was much less than that of the oleoyl chains, and occurred predominantly as PC and lyso-PC (0.6%, compared with 0.4% as bile acids in 6 h). Breath analyses demonstrated that a considerable fraction of both acyl chains was oxidized to CO2 and expired: 25.1% of the administered label for oleoyl chains and 13.4% for palmitoyl chains respectively in a 4 h period. The results of this study indicate that liposomal PC is only minimally secreted into bile via a direct pathway; the bulk is extensively degraded in the liver. Resulting products are partly secreted into bile, as bile acid or as resynthesized PC. There appears to be a quantitative difference in the metabolism of oleoyl and palmitoyl acyl chains.

scholarly journals Regulation of Bacillus subtilis DesK thermosensor by lipids

2013 ◽  
Vol 451 (2) ◽  
pp. 269-275 ◽  
Author(s):  
Mariana Martín ◽  
Diego de Mendoza
Keyword(s):  
Bacillus Subtilis ◽  
Lipid Composition ◽  
Group Structure ◽  
Acyl Chain ◽  
Kinase Domain ◽  
Head Group ◽  
Fatty Acyl Chain ◽  
Synthetic Approach ◽  
Membrane Thickness

Temperature sensing is essential for the survival of living cells. The membrane-bound thermosensor DesK from Bacillus subtilis is a key representative of histidine kinases receptors able to remodel membrane lipid composition when the temperature drops below ~30°C. Although the receptor is well studied, a central issue remains: how does the compositional and functional diversity of the surrounding membrane modulate receptor function? Reconstituting full-length DesK into proteoliposomes of well-defined and controlled lipid composition represents a minimal synthetic approach to systematically address this question. Thus DesK has been reconstituted in a variety of phospholipid bilayers and its temperature-regulated autokinase activity determined as function of fatty acyl chain length, lipid head-group structure and phase preference. We show that the head group structure of lipids (both in vitro and in vivo) has little effect on DesK thermosensing, whereas properties determined by the acyl chain of lipids, such as membrane thickness and phase separation into coexisting lipid domains, exert a profound regulatory effect on kinase domain activation at low temperatures. These experiments suggest that the non-polar domain of glycerolipids is essential to regulate the allosteric structural transitions of DesK, by activating the autophosphorylation of the intracellular kinase domain in response to a decrease in temperature.

scholarly journals Interaction of metalloporphyrins with lipid bilayers, a calorimetric study

2011 ◽  
Vol 34 (1) ◽  
pp. 11-14
Author(s):  
Katarzyna Pamin ◽  
Jan Połtowicz ◽  
Joanna Kiełkowicz ◽  
Andrzej Hendrich
Keyword(s):  
Experimental Data ◽  
Phase Transitions ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Electrostatic Interactions ◽  
Acyl Chain ◽  
Head Group ◽  
Calorimetric Study ◽  
Polar Head Group ◽  
Polar Head

Interaction of metalloporphyrins with lipid bilayers, a calorimetric studyThe interaction of three metalloporphyrins, containing manganese, iron and cobalt atoms, with lipid bilayers composed of neutral (DPPC) or charged (DMPG) phospholipids were studied by means of scanning differential calorimetry. We found only minute effects exerted by studied compounds on DPPC, while phase transitions of charged DMPG were seriously affected by porphyrins. Analysis of experimental data revealed that due to the electrostatic interactions DMPG bilayers are perturbed not only in the polar head group region. Putative rearrangements of the polar heads packing affects also the acyl chain region of this lipid bilayer. Perturbation of DMPG polar heads induced by porphyrin in complex with manganese atoms is bigger than that induced by other porphyrins.

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