Glyceryl Esters Research Articles

Lipase-catalyzed enantioselective hydrolysis of N-protected racemic non-protein amino acid esters

Porcine pancreatic lipase (PPL)-catalyzed enantioselective hydrolysis of N-benzyloxycarbonyl-dl-amino acid esters (Z-dl-AA-ORs) was studied for the optical resolution of a variety of non-protein amino acids. The ester moiety (R) of the substrate affected the rate of hydrolysis significantly. The glyceryl (Gl) and carbamoylmethyl (Cam) esters were found to be highly reactive substrates. The hydrolysis of the Gl esters (Z-dl-AA-OGls) of both aliphatic and aromatic amino acids was examined in acetonitrile containing 70% (v/v) of 0.02 M phosphate buffer (pH 7.0) at 30°C. With all amino acids tested, the corresponding l-enantiomers were hydrolyzed preferentially. PPL favored aromatic amino acids, such as phenylalanine and p-chlorophenylalanine, leading to completion of the hydrolysis within 20 min with excellent enantioselectivities (E>100). The PPL-catalyzed hydrolysis of the corresponding Cam esters (Z-dl-AA-OCams) was also examined under the same reaction conditions. Although the hydrolysis of the Cam esters was rapid, the l-enantioselectivities were rather poor with aromatic amino acids, such as 2-phenylglycine and homophenylalanine.

Fungal-Stressed Germination of Black Soybeans Leads to Generation of Oxooctadecadienoic Acids in Addition to Glyceollins

Microbial-stressed germination of black soybeans leads to generation of a group of oxylipins, oxooctadecadienoic acids (KODEs, including 13- Z, E-KODE, 13- E, E-KODE, 9- E, Z-KODE, and 9- E, E-KODE), and their respective glyceryl esters in addition to glyceollins, a known phytoalexins present in wild and fungi-infected soybeans. Four fungi, Aspergillus niger, Aspergillus oryzae, Rhizopus oligosporus, and white rice yeast ( Aspergillus niger wry), were applied to compare their efficiency on inducing these compounds during black soybean germination. Overall, R. oligosporus, the starter culture used in tempeh fermentation, gives the highest amounts of KODEs and glyceollins. The glyceollins and KODEs were isolated by preparative HPLC, and the structures were determined by (1)H NMR, UV-Vis, and MS spectra. On the basis of the unequal distribution of the KODEs isomers, an enzymatic reaction, instead of a nonenzymatic free radical chain reaction, is responsible for their formations. Together with other oxylipins and glyceollins, the KODEs may contribute to the soybean's defensive response to fungal infection via reaction with protein thiol groups and cell membranes. The stress-germinated black soybeans may be used as ingredients for further processing of novel functional food products with unique nutritional and flavor profiles.

COX‐2 oxidative metabolite of endocannabinoid 2‐AG enhances excitatory glutamatergic synaptic transmission and induces neurotoxicity

Neuroinflammation has been implicated in the pathogenesis of neurodegenerative diseases. Cyclooxygenase-2 (COX-2), an inducible enzyme converting arachidonic acid (AA) to prostaglandins, is the key player in neuroinflammation. It has been long thought that the COX-2-mediated neuronal injury/degeneration is attributed to the increased production of AA-derived prostaglandins. Recent studies show that endogenous cannabinoid 2-arachidonoylglycerol (2-AG) is a natural substrate for COX-2, and it can be oxygenated by COX-2 to form prostaglandin glyceryl esters. In this study, we demonstrate that prostaglandin E(2) glyceryl ester (PGE(2)-G), a major COX-2 oxidative metabolite of 2-arachidonoylglycerol, enhanced hippocampal glutamatergic synaptic transmission indicated by the increased frequency of miniature excitatory post-synaptic currents, and induced neuronal injury/death revealed by the terminal transferase dUTP nick end labeling staining and caspase 3 activation. The actions of PGE(2)-G are not mediated via a cannabinoid receptor 1, but mediated through ERK, p38 mitogen-activated protein kinase, IP(3), and NF-kappaB signal transduction pathways. In addition, the PGE(2)-G-induced neurotoxicity is attenuated by blockade of the NMDA receptors. Our results suggest that the COX-2 oxidative metabolism of endocannabinoids is an important mechanism contributing to the inflammation-induced neurodegeneration.

Detection of the abundance of diacylglycerol and triacylglycerol molecular species in cells using neutral loss mass spectrometry

Triacylglycerols (TAGs) are neutral lipids present in all mammalian cells as energy reserves, and diacylglycerols (DAGs) are present as intermediates in phospholipid biosynthesis and as signaling molecules. The molecular species of TAGs and DAGs present in mammalian cells are quite complex, and previous investigations revealed multiple isobaric species having molecular weights at virtually every even mass between 600 and 900 Da, making it difficult to assess changes of individual molecular species after cell activation. A method has been developed, using tandem MS and neutral loss scanning, to quantitatively analyze changes in those glyceryl ester molecular species containing identical fatty acyl groups. This was carried out by neutral loss scanning of 18 common fatty acyl groups where the neutral loss corresponded to the free carboxylic acid plus NH 3. Deuterium-labeled internal standards were used to normalize the signal for each nominal [M + NH 4] + ion undergoing this neutral loss reaction. This method was applied in studies of TAGs in RAW 264.7 cells treated with the toll-like receptor 4 ligand Kdo 2–lipid A. A 50:1-TAG containing 18:1 was found to increase significantly over a 24-h time course after Kdo 2–lipid A exposure, whereas an isobaric 50:1-TAG containing 16:1 did not change relative to controls.

Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin‐ethanolamides) in the feline iris

The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants. In the feline iris, AGN 204396 produced a rightward shift of the dose-response curves for prostamide F2alpha and the prostamide F2alpha analog bimatoprost but did not block the effects of PGF2alpha and synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist. AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810 efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist. Al-8810 did not block prostamide F2alpha activity. Finally, AGN 204396 did not block PGE2-glyceryl ester activity. The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2alpha and PGE2-glyceryl ester.

Optimization of Metalworking Fluid Microemulsion Surfactant Concentrations for Microfiltration Recycling

Microfiltration can be used as a recycling technology to increase metalworking fluid (MWF) life span, decrease procurement and disposal costs, and reduce occupational health risks and environmental impacts. The cost-effectiveness of the process can be increased by minimizing fouling interactions between MWFs and membranes. This paper reports on the development of a microfiltration model that establishes governing relationships between MWF surfactant system characteristics and microfiltration recycling performance. The model, which is based on surfactant adsorption/desorption kinetics, queueing theory, and coalescence kinetics of emulsion droplets, is verified experimentally. An analysis of the model and supporting experimental evidence indicates that the selection of surfactant systems minimally adsorb to membranes and lead to a high activation energy of coalescence results in a higher MWF flux through microfiltration membranes. The model also yields mathematical equations that express the optimal concentrations of anionic and nonionic surfactants with which microfiltration flux is maximized for a given combination of oil type, oil concentration, and surfactant types. Optimal MWF formulations are demonstrated for a petroleum oil MWF using a disulfonate/ ethoxylated alcohol surfactant package and for several vegetable oil MWFs using a disulfonate/ethoxylated glyceryl ester surfactant package. The optimization leads to flux increases ranging from 300 to 800% without impact on manufacturing performance. It is further shown that MWF reformulation efforts directed toward increasing microfiltration flux can have the beneficial effect of increasing MWF robustness to deterioration and flux decline in the presence of elevated concentrations of hardwater ions.

Misidentification of prostamides as prostaglandins

Prostaglandins and endogenous cannabinoid metabolites share the same lipid backbone with differing polar head groups at exactly the position through which a large molecule is attached to provide antigenicity and thus raise antisera. Hence, we hypothesized that antisera raised against prostaglandins linked to a large molecule such as BSA at the carboxyl functional group would also recognize endogenous cannabinoid metabolites and lead to highly misleading interpretations of data. We found major cross-reactivity of commercial antisera raised to prostaglandins with endocannabinoid metabolites. Furthermore, in a well-characterized cell line (WISH) or primary amnion tissue explants, endocannabinoid treatment led to increased production of endocannabinoid metabolites as opposed to primary prostaglandins. This was apparent only after separation of products by thin-layer chromatography, because they measured as prostaglandins by radioimmunoassay. These findings have major implications for our interpretation of data in situations in which these prostaglandin-like molecules are formed, and they stress the need for chromatographic or spectrometric confirmation of prostaglandin production detected by antibody-based methods.

Glycerylprostaglandin Synthesis by Resident Peritoneal Macrophages in Response to a Zymosan Stimulus

Cyclooxygenase (COX)-2 oxygenates arachidonic acid (AA) and 2-arachidonylglycerol (2-AG) to endoperoxides, which are subsequently transformed to prostaglandins (PGs) and glycerylprostaglandins (PG-Gs). PG-G formation has not been demonstrated in intact cells treated with a physiological agonist. Resident peritoneal macrophages, which express COX-1, were pretreated with lipopolysaccharide to induce COX-2. Addition of zymosan caused release of 2-AG and production of the glyceryl esters of PGE2 and PGI2 over 60 min. The total quantity of PG-Gs (16 +/- 6 pmol/10(7) cells) was much lower than that of the corresponding PGs produced from AA (21,000 +/- 7,000 pmol/10(7) cells). The differences in PG-G and PG production were partially explained by differences in the amounts of 2-AG and AA released in response to zymosan. The selective COX-2 inhibitor, SC236, reduced PG-G and PG production by 49 and 17%, respectively, indicating a significant role for COX-1 in PG-G and especially PG synthesis. Time course studies indicated that COX-2-dependent oxygenation rapidly declined 20 min after zymosan addition. When exogenous 2-AG was added to macrophages, a substantial portion was hydrolyzed to AA and converted to PGs; 1 microm 2-AG yielded 820 +/- 200 pmol of PGs/10(7) cells and 78 +/- 41 pmol of PG-Gs/10(7) cells. SC236 reduced PG-G and PG production from exogenous 2-AG by 88 and 76%, respectively, indicating a more significant role for COX-2 in the utilization of exogenous substrate. In conclusion, lipopolysaccharide-pretreated macrophages produce PG-Gs from endogenous 2-AG during zymosan phagocytosis, but PG-G formation is limited by substrate hydrolysis and inactivation of COX-2.

Simultaneous analysis of prostaglandin glyceryl esters and prostaglandins by electrospray tandem mass spectrometry

A high-performance liquid chromatography (HPLC) positive-ion electrospray ionization tandem mass spectrometry method for the quantification of prostaglandin glyceryl esters (PG-Gs), a newly discovered class of eicosanoids, is described. All four PG-Gs (PGE 2-G, PGD 2-G, PGF 2α-G, and 6-keto-PGF 1α-G) and the prostaglandins (PGs) that are formed by their hydrolysis are simultaneously quantified. Analytes were purified via reverse-phase solid-phase extraction, separated by reverse-phase HPLC, and quantified on a triple-quadrupole mass spectrometer using selected reaction monitoring. Quantification was achieved by stable isotope dilution employing penta-deuterated (PG-Gs) or tetra-deuterated (PGs) analogs. Analyte recovery from cell culture medium was >43% for all analytes at four different concentration levels. The limit of quantification is in the range of 25 fmol on-column for each analyte and the analytes exhibit a linear response over approximately a 500-fold range. This method allows simultaneous profiling of several PG-Gs and PGs without multistep sample purification or derivatization.

A new sunscreen of the cinnamate class: Synthesis and enzymatic hydrolysis evaluation of glyceryl esters of p-methoxycinnamic acid

Glyceryl esters of p-methoxycinnamic acid, 1,3-dipalmitoyl-2- p-methoxycinnamoyl-1,2,3-propanetriol and 1,3-dioctanoyl-2- p-methoxycinnamoyl-1,2,3-propanetriol were synthesised in an attempt to increase substantivity and decrease eventual undesirable effects of sunscreens of this class. To assess if the glyceryl esters could present a higher stability towards hydrolysis by lipases in the stratum corneum, hydrolysis rates were determined in vitro using a commercial fungal lipase from Rhizomucor miehei. Results presented herein show that the glyceryl esters have similar λ max and ɛ values to sunscreens of the cinnamate class. The ester 1,3-dipalmitoyl-2- p-methoxycinnamoyl-1,2,3-propanetriol presented a 2.8 times lower hydrolysis rate by lipase, in vitro, than the commercial sunscreen 2-ethylhexyl- p-methoxycinnamate (alkyl ester). This finding suggests that this triacylglycerol can possibly have a longer retention time in the skin and consequently promote a more intense and effective antisolar action than the commercial sunscreen.

A facile synthesis of aminohydroxy triglycerides from new crop oils

AbstractVegetable oils as the main source of plant lipids are currently generating much interest as renewable industrial feedstocks for nonfood industrial applications both as biobased lubricants and biodiesel fuels. But of particular interest for us is use of new crop oils in novel industrial applications. These oils, in general, are glyceryl esters with olefinic bonds, which are readily functionalizable. Aminated lipids are important intermediates in many applications including pharmaceutical formulations because they have a modifying effect on cell membranes. We have exploited the nucleophilic property of the carbon‐carbon double bonds in two seed oils to generate the oxirane derivatives of the lipids. Ring opening of the epoxy intermediates with amines under anhydrous ZnCl2 catalysis is facile, and the reaction proceeds smoothly at moderate temperatures to given the aminohydroxy TG of milkweed and salicornia oils.

Organic composition of aerosol particulate matter during a haze episode in Kuala Lumpur, Malaysia

The solvent-extractable compounds of urban airborne particulate matter were analyzed to determine the distributions of homologous and biomarker tracers. Samples were collected by high-volume air filtration during the haze episode of 1997 around the University of Malaya campus near Petaling Jaya, a suburb of Kuala Lumpur, Malaysia. These results show that the samples contain n-alkanes, n-alkan-2-ones, n-alkanols, methyl n-alkanoates, n-alkyl nitriles, n-alkanals, n-alkanoic acids, levoglucosan, PAHs, and UCM as the dominant components, with minor amounts of terpenoids, glyceryl esters and sterols, all derived from natural biogenic sources (vascular plant wax), from burning of biomass, and from anthropogenic utilization of fossil fuel products (lubricating oil, vehicle emissions, etc.). Some compositional differences are observed in the samples and greater atmospheric concentrations were found for almost all organic components in the samples collected near a roadway. The results interpreted in terms of major sources are due to local build-up of organic contaminants from vehicular emissions, smoke from biomass burning, and natural background as a result of the atmospheric stability during the haze episodes. The organic components transported in from areas outside the region, assuming all smoke components are external to the city, amount to about 30% of the total organic particle burden.

The glyceryl ester of prostaglandin E2mobilizes calcium and activates signal transduction in RAW264.7 cells

Glyceryl prostaglandins (PG-Gs) are generated by the oxygenation of the endocannabinoid, 2-arachidonylglycerol, by cyclooxygenase 2. The biological consequences of this selective oxygenation are uncertain because the cellular activities of PG-Gs have yet to be defined. We report that the glyceryl ester of PGE(2), PGE(2)-G, triggers rapid, concentration-dependent Ca(2+) accumulation in a murine macrophage-like cell line, RAW264.7. Ca(2+) mobilization is not observed after addition of PGE(2), PGD(2)-G, or PGF(2alpha)-G but is observed after addition of PGF(2alpha). Moreover, PGE(2)-G, but not PGE(2), stimulates a rapid but transient increase in the levels of inositol 1,4,5-trisphosphate (IP(3)) as well as the membrane association and activation of PKC. PGE(2)-G induces a concentration-dependent increase in the levels of phosphorylated extracellular signal regulated kinases 1 and 2 through a pathway that requires the activities of PKC, IP(3) receptor, and phospholipase C beta. The results indicate that PGE(2)-G triggers Ca(2+) mobilization, IP(3) synthesis, and activation of PKC in RAW264.7 macrophage cells at low concentrations. These responses are independent of the hydrolysis of PGE(2)-G to PGE(2).

Further chemical studies on the Antarctic nudibranch Austrodoris kerguelenensis: new terpenoid acylglycerols and revision of the previous stereochemistry

The diterpenoid acylglycerol fraction from an extract of the mantle of a new collection of the Antarctic dorid gastropod mollusc Austrodoris kerguelenensis has been chemically analysed. Two novel 2-monoacylglycerols 9 and 12 , along with known 1,2-diacyl glyceryl esters 5 and 6 , now reassigned as 7 and 8 , have been isolated. The linkage of a diterpenoid moiety at C-2 of glycerol characterizes all the compounds. Because the R absolute stereochemistry at C-2 of glycerol has been established for the corresponding 1,3-glyceryl esters 1 and 2 , derived from 7 and 8 by acyl-migration of the terpenoid moiety from C-2 to C-3, our finding implies that 1,2-derivatives from Antarctic nudibranchs have the same S stereochemistry as all 1,2- sn-diacylglycerols from the other dorids.

Glycerol and glyceryl esters of ω-hydroxyacids in cutins

Cutins from the leaves and fruits of seven plant species were depolymerized by NaOCH 3-methanolysis. The monomers that were released mostly included C16 and C18 ω-hydroxyacids with mid-chain oxygenated substitutions, namely epoxy and hydroxyl groups. Glycerol was also solubilized as a monomer in quantities that ranged from 1 to 14% of the methanolysates. Partial depolymerization of three cutins by CaO-methanolysis released the same monomers as had been obtained in the previous reaction, as well as small quantities of 1- and 2-monoacylglyceryl esters of ω-hydroxyacids. Molar proportions of glycerol permit the esterification of a significant part of the aliphatic ω-hydroxyacids, thereby possibly playing a major role in the polyester structure of cutin. Glycerol had not previously been known to form part of the cutin polymer.

15-Lipoxygenase Metabolism of 2-Arachidonylglycerol: GENERATION OF A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR α AGONIST

The recent demonstrations that cyclooxygenase-2 and leukocyte-type 12-lipoxygenase (LOX) efficiently oxygenate 2-arachidonylglycerol (2-AG) prompted an investigation into related oxygenases capable of metabolizing this endogenous cannabinoid receptor ligand. We evaluated the ability of six LOXs to catalyze the hydroperoxidation of 2-AG. Soybean 15-LOX, rabbit reticulocyte 15-LOX, human 15-LOX-1, and human 15-LOX-2 oxygenate 2-AG, providing 15(S)-hydroperoxyeicosatetraenoic acid glyceryl ester. In contrast, potato and human 5-LOXs do not efficiently metabolize this endocannabinoid. Among a series of structurally related arachidonyl esters, arachidonylglycerols serve as the preferred substrates for 15-LOXs. Steady-state kinetic analysis demonstrates that both 15-LOX-1 and 15-LOX-2 oxygenate 2-AG comparably or preferably to arachidonic acid. Furthermore, 2-AG treatment of COS-7 cells transiently transfected with human 15-LOX expression vectors or normal human epidermal keratinocytes results in the production and extracellular release of 15-hydroxyeicosatetraenoic acid glyceryl ester (15-HETE-G), establishing that lipoxygenase metabolism of 2-AG occurs in an eukaryotic cellular environment. Investigations into the potential biological actions of 15-HETE-G indicate that this lipid, in contrast to its free-acid counterpart, acts as a peroxisome proliferator-activated receptor alpha agonist. The results demonstrate that 15-LOXs are capable of acting on 2-AG to provide 15-HETE-G and elucidate a potential role for endocannabinoid oxygenation in the generation of peroxisome proliferator-activated receptor alpha agonists.

Synthesis of glycero amino acid-based surfactants. Part 2.1 Lipase-catalysed synthesis of 1-O-lauroyl-rac-glycero-3-O-(Nα-acetyl-L-amino acid) and 1,2-di-O-lauroyl-rac-glycero-3-O-(Nα-acetyl-L-amino acid) derivatives

An enzymatic procedure for the synthesis of mono- and dilauroylated amino acid glyceride conjugates is presented. The reaction consisted of the lipase-catalysed esterification of one or two hydroxy groups of the amino acid glyceryl ester derivatives by lauric acid. Solvent-free media with continuous removal of the water produced at atmospheric pressure were the reaction systems of choice. It is found that the mono- and dilauroylation yields and enzymatic activity depended crucially on the reaction temperature, the molar ratio of lauric acid to amino acid glyceryl ester, and concentration of phosphate salts using Candida antarctica (Novozym® 435) and Rhizomucor miehei (Lipozyme® IM) lipases as catalysts. These reaction variables are identified and studied systematically using Boc–Arg–OGl as a model substrate and modulated accordingly for the target amino acid-based compounds. As in conventional glycerides, spontaneous intramolecular acyl-migration reactions are observed for the lauroyl and aminoacyl moieties of the glycerol backbone. This reaction led to a number of regioisomers, which are identified and quantified by mono- and bidimensional NMR techniques. The method developed allowed us to prepare glycero conjugates of arginine, aspartic acid, glutamic acid, asparagine, glutamine and tyrosine in isolated yields of the regioisomeric mixtures ranging from 22 to 69%.

Synthesis of glycero amino acid-based surfactants. Part 1. Enzymatic preparation of rac-1-O-(Nα-acetyl-l-aminoacyl)glycerol derivatives

An enzymatic procedure for the selective synthesis of a number of Nα-protected amino acid glyceryl esters is presented. Using Nα-Boc-arginine as a model substrate, changes in product yield are examined for the following reaction variables: aqueous buffer content, pH, biocatalyst configuration (free or deposited), enzyme concentration and synthetic approach (thermodynamically or kinetically controlled synthesis). The best yields (61–89%) are obtained at 50 °C in glycerol containing a range of aqueous buffer from 0 to 10% (v/v). Readily available industrial proteases and lipases are used as catalysts. The method allowed us to selectively acylate one of the primary hydroxy groups of the glycerol with the carboxylate groups of the amino acid. In the case of aspartic acid and glutamic acid, selective esterification of the α-carboxylate group is achieved. None of the enzymes tested could differentiate between the two enantiotopic hydroxymethyl groups of glycerol, giving diastereoisomeric mixtures in all cases.

Selective oxygenation of the endocannabinoid 2-arachidonylglycerol by leukocyte-type 12-lipoxygenase.

The endogenous cannabinoid system appears to serve vascular, neurological, immunological, and reproductive functions. The identification of 2-arachidonylglycerol (2-AG) as an endogenous ligand for the central (CB1) and peripheral (CB2) cannabinoid receptors has prompted interest in enzymes capable of modifying or inactivating this endocannabinoid. Porcine leukocyte 12-liopoxygenase (12-LOX) oxygenated 2-AG to the 2-glyceryl ester of 12(S)-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12-HPETE-G). The k(cat)/K(M) for oxygenation of 2-AG was 40% of the value for arachidonic acid. In contrast to the results with leukocyte 12-LOX, 2-AG oxygenation was not detected with platelet-type 12-LOX. Among a series of structurally related arachidonyl esters, 2-AG served as the preferential substrate for leukocyte 12-LOX. 12(S)-Hydroxyeicosa-5,8,10,14-tetraenoic acid glyceryl ester (12-HETE-G) was produced following addition of 2-AG to COS-7 cells transiently transfected with leukocyte 12-LOX. These results demonstrate that leukocyte-type 12-LOX efficiently oxidizes 2-AG in vitro and in intact cells, suggesting a role for this oxygenase in the endogenous cannabinoid system.

Low Molecular Weight Gelators for Organic Fluids: Gelation Using a Family of Cyclo(dipeptide)s

Simple cyclo(dipeptide)s consisting of diverse amino acids are able to cause physical gelation in a wide variety of organic fluids, including edible oils, glyceryl esters, alcohols, and aromatic molecules. Minimum gel concentrations, FTIR spectroscopy, NMR spectroscopy, and electron micrograph are used to characterize gel phenomenon. The intermolecular hydrogen bonding between N–H and C=O in cyclo(dipeptide)s plays an important role in gelation. FTIR and X-ray diffraction data suggest that the aggregate responsible for gel is an assembly of hydrogen-bonded molecular ladders, which are initially formed from numerous molecules through intermolecular hydrogen bonding. The ladder-like aggregates are intertwined and interlocked, and finally immobilize organic fluids. The gelation ability is discussed in connection with the three-component solubility parameters of solvents.