Thin-layer chromatographic study of the metabolites of erythromycins in the Wistar rat

The metabolites of erythromycin A, anhydroerythromycin A, N-demethylerythromycin A and erythromycin B in the Wistar rat were studied by thin-layer chromatography. In some experiments germ-free rats, rats with a cannulated bile duct and a gastrectomized rat were used. The erythromycins examined were shown to undergo two principal changes, N-demethylation and acid-catalysed degradation. It was demonstrated that the stomach and the liver are not the sole sites of acid degradation and demethylation of erythromycins, respectively. Erythromycin A gives three principal metabolites, anhydroerythromycin A, anhydro-N-demethylerythromycin A and N-demethylerythromycin A, and erythromycin A enol ether and N-demethylerythromycin A enol ether are present to a minor extent. 5-O-Desosaminylerythronolide A was also identified, suggesting the presence of an erythromycin glycosidase.     

A correlated force-optical study on the self-assembly behavior of annexin V on model membranes: effect of dye conjugation

We have examined the self-assembled membrane-bound aggregates of two annexin V (A5) dye conjugates and compared them to those from native A5. Native A5 and FITC-labeled A5 (A5-FITC) both formed discrete well-defined crystalline monolayer domains of p6 symmetry. However, A5-FITC also showed additional domains with a corrugated appearance not observed in native A5. In contrast, Cy3-labeled A5 (A5-Cy3) showed a mixture of crystalline monolayer and irregular multilayered domains, with the ratio of the two types varying significantly from sample to sample, and also required a much longer incubation time than native A5 and A5-FITC. When A5-FITC and A5-Cy3 were co-incubated on the same bilayer, well-defined crystalline monolayer domains containing both A5-FITC and A5-Cy3 were consistently observed at a much shorter incubation time than that of pure A5-Cy3 alone, indicating that A5-FITC facilitates the inclusion of A5-Cy3. These results suggest that dye labels can affect A5 2D self-assembly and crystal formation on membrane surfaces.     

Two-dimensional lattice Monte Carlo simulation of the compatibility of A/B/functionalized A ternary polymer mixtures coupled with chemical reaction

Compatibility of A/B and functionalized A ternary polymer mixtures was studied by Monte Carlo simulation in a two-dimensional lattice. Polymer A was a nonreactive polymer, whereas polymer B was a reactive polymer and immiscible with polymer A. Functionalized polymer A could react with the end group of polymer B, leading to the formation of block copolymers. Simulation results showed the phase domain sizes dropped considerably with increasing functionalized polymer A content, indicating that the compatibility between polymer A and B could be markedly improved with the introduction of functionalized polymer A. Moreover, it was shown that the resulting block copolymers tended to distribute at the phase interface between polymer A and B, and the block copolymer conformation depended on the structures of polymer B and functionalized polymer A. In case 1, i.e., both polymer B and functionalized polymer A were with single end group, it could be found that the block A and block B of resulting A–B copolymer inserted into polymer A and polymer B phase domains, respectively. In case 2, i.e., functionalized polymer A was with single end group and polymer B was with double end groups, it was found that the resulting A–B–A triblock copolymer tended to connect two neighbor separated polymer A phase domains. However, in case 3, namely functionalized polymer A was with double end groups and polymer B was with single end group, it was found that the resulting B–A–B triblock copolymer was likely to form a folding conformation. These lead to the different compatibilizing effects for different polymer structures. Comparing with case 1 and case 2, functionalized polymer A with double end groups (case 3) had less effective to compatibilize the A/B polymer blends. For the purpose of comparison, same simulations were carried out in a three-dimensional lattice. The results showed the compatibility behavior of the mixtures was similar to those in the two-dimensional lattice with the addition of functionalized polymer A. However, the conformation of the resulting block copolymers was different from that in the two-dimensional lattice.     

High-performance liquid chromatographic separation of subcomponents of antimycin A

Using a reversed-phase high-performance liquid chromatographic (HPLC) technique, a mixture of antimycins A was separated into eight hitherto unreported subcomponents, A1a, A1b, A2a, A2b, A3a, A3b, A4a, and A4b. Although a base-line resolution of the known four major antimycins A1, A2, A3, and A4 was readily achieved with mobile phases containing acetate buffers, the separation of the new antibiotic subcomponents was highly sensitive to variation in mobile phase conditions. The type and composition of organic modifers, the nature of buffer salts, and the concentration of added electrolytes had profound effects on capacity factors, separation factors, and peak resolution values. Of the numerous chromatographic systems examined, a mobile phase consisting of methanol-water (70:30) and 0.005 M tetrabutylammonium phosphate at pH 3.0 yielded the most satisfactory results for the separation of the subcomponents. Reversed-phase gradient HPLC separation of the dansylated or methylated antibiotic compounds produced superior chromatographic characteristics and the presence of added electrolytes was not a critical factor for achieving separation. Differences in the chromatographic outcome between homologous and structural isomers were interpreted based on a differential solvophobic interaction rationale. Preparative reversed-phase HPLC under optimal conditions enabled isolation of pure samples of the methylated antimycin subcomponents for use in structural studies.     

Innate immune responses of synthetic lipid A derivatives of Neisseria meningitidis

Differences in the pattern and chemical nature of fatty acids of lipid A of Neisseria meningitides lipooligosaccharides (LOS) and Escherichia coli lipopolysaccharides (LPS) may account for differences in inflammatory properties. Furthermore, there are indications that dimeric 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) moieties of LOS and LPS enhance biological activities. Heterogeneity in the structure of lipid A and possible contaminations with other inflammatory components have made it difficult to confirm these observations. To address these problems, a highly convergent approach for the synthesis of a lipid A derivative containing KDO has been developed, which relies on the ability to selectively remove or unmask in a sequential manner an isopropylidene acetal, 9-fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonate (Alloc), azide, and thexyldimethylsilyl (TDS) ether. The strategy was employed for the synthesis of N. meningitidis lipid A containing KDO (3). Mouse macrophages were exposed to the synthetic compound and its parent LOS, E. coli lipid A (2), and a hybrid derivative (4) that has the asymmetrical acylation pattern of E. coli lipid A, but the shorter lipids of meningococcal lipid A. The resulting supernatants were examined for tumor necrosis factor alpha (TNF-alpha) and interferon beta (IFN-beta) production. The lipid A derivative containing KDO was much more active than lipid A alone and just slightly less active than its parent LOS, indicating that one KDO moiety is sufficient for full activity of TNF-alpha and IFN-beta induction. The lipid A of N. meningitidis was a significantly more potent inducer of TNF-alpha and IFN-beta than E. coli lipid A, which is due to a number of shorter fatty acids. The compounds did not demonstrate a bias towards a MyD88- or TRIF-dependent response.     

Preparation, phototoxicity and biodistribution studies of anti-carcinoembryonic antigen monoclonal antibody-phthalocyanine conjugates

Immunophototherapy of cancer combines the specificity of a monoclonal antibody (MAb) to an overexpressed tumor marker with the phototoxic properties of a conjugated dye. Aluminum tetrasulfophthalocyanine (AlPcS4) was covalently coupled to a 35A7 MAb directed against carcinoembryonic antigen (CEA) via a five-carbon spacer chain (A1) to yield conjugates with a molar ratio ranging from 5 to 16 mol of AlPcS4 per mol of 35A7 MAb. Conjugates were labeled with radioiodine for characterization. The immunoreactivity of the conjugates, determined in a direct binding assay on CEA coupled to sepharose, was not modified by the coupled AlPcS4A1 molecules. In vivo, these conjugates were evaluated in nude mice bearing human colon carcinoma xenografts (T380). 35A7 MAb-(AlPcS4A1)5, 35A7 MAb-(AlPcS4A1)12 and 35A7 MAb-(AlPcS4A1)16 conjugates displayed a tumor uptake of 35 +/- 5.0%, 40 +/- 5.7% and 32 +/- 3.3% of the injected dose per gram of tumor tissue, respectively, corresponding to an uptake of 97%, 104% and 91% as compared to that of the unconjugated 35A7 MAb. In each experimental group, the tumor-to-normal tissue ratios obtained with the conjugates were almost identical to those obtained with unconjugated 35A7 MAb. Average values of 1.8, 7 and about 30 were obtained for blood, liver and muscle, respectively. Phototoxic efficacy of the 35A7 MAb-(AlPcS4A1)12 conjugate was demonstrated in vitro on the LoVo cell line giving a 91% growth inhibition for a 2.50 micrograms/mL AlPcS4A1 concentration. We conclude that these conjugates demonstrate clear in vivo tumor-seeking capacity and in vitro photocytotoxic properties. Such conjugates could thus be promising candidate drugs for clinical photodynamic therapy of cancers expressing CEA.     

Base pair recognition of the stereochemically alpha-substituted gamma-turn of pyrrole/imidazole hairpin polyamides

Recognition of the sequences 5'-NGCACA-3' (N = T, A, C, G) by pyrrole/imidazole polyamides with (R/S)-alpha-hydroxyl/alpha-amino-substituted gamma-aminobutyric acid as a gamma-turn was investigated. Four novel polyamides, 2, 3, 4, and 5, including (R)-alpha-hydroxyl-gamma-aminobutyric acid (gammaRO), (S)-alpha-hydroxyl-gamma-aminobutyric acid (gammaSO), (R)-alpha,gamma-diaminobutyric acid (gammaRN), and (S)-alpha,gamma-diaminobutyric acid (gammaSN) residues, respectively, were synthesized, and their binding affinity to T.A, A.T, G.C, and C.G base pairs at turn position was studied by the surface plasmon resonance (SPR) technique. SPR data revealed that polyamide 3, AcImbetaImPy-gammaSO-ImPybetaPy-beta-Dp, with a gammaSO turn, possesses a marked binding preference for T.A over A.T with a 25-fold increase in specificity, despite low binding affinity relative to 2, with a gammaRO turn. Similarly, AcImbetaImPy-gammaSN-ImPybetaPy-beta-Dp (5), with a gammaSN-turn, gives rise to a 8.7-fold increase in specificity for T.A over A.T. Computer-assisted molecular modeling suggests that 3 binds more deeply in the minor groove of the T.A base pair relative to the A.T base pair, allowing hydrogen bonding to O2 of the thymine at the turn position, which explains the SPR results. These results suggest that gammaSO and gammaSN may function as T-recognition units at the turn position, as well as a gamma-turn in the discrimination of polyamides.     

Recent research and development of DYRK1A inhibitors

Dual specificity tyrosine phosphorylation regulated kinase 1 A(DYRK1 A) is an evolutionarily conserved protein kinase belonging to the CMGC kinase family, which is closely related to Down syndrome(DS)and Alzheimer’s disease(AD). In recent years, not only the treatment of diabetes, but also the treatment of cancer gradually focuses on targeting DYRK1 A. Therefore, a series of DYRK1 A inhibitors have been developed to treat relevant diseases and clarify their treatment mechanism furtherly. DYRK1 A...     

Unexpected formation of an azetidine-carborane derivative by dehydration of N-(1,12-dicarba-closo-dodecaboran-1-yl)formamide. The first X-ray structure of a 2,3-bis(imino)azetidine

Efforts to dehydrate (1,12-dicarba-closo-dodecaboran(12)-1-yl)formamide (a = 6.685(2) A, b = 12.877(4) A, c = 12.547(4) A, alpha = gamma = 90 degrees, beta = 90.724(11) degrees, V = 1080.8(6) A(3), Z = 4) resulted in the formation of a series of unexpected products. Addition of the Burgess reagent to the formamide, for example, led to the isolation of the corresponding methyl carbamate (a = 11.529(8) A, b = 11.529(8) A, c = 11.402(12) A, alpha = beta = gamma = 90 degrees, V = 1516(2) A(3), Z = 4), while treatment with triphosgene, a well-known dehydrating agent, resulted in the formation of a highly unusual 2,3-bis(p-carboranylimino)azetidine derivative. This particular compound, in the presence of Re(I), was hydrolyzed to give the corresponding amide, which is the first example of a 2,3-bis(imino)azetidine that has been characterized crystallographically (a = 38.496(13) A, b = 11.920(4) A, c = 27.523(10) A, beta = 127.050(5) degrees, V = 10079(6) A(3), Z = 8).     

Mechanism for activation of triosephosphate isomerase by phosphite dianion: the role of a hydrophobic clamp

The role of the hydrophobic side chains of Ile-172 and Leu-232 in catalysis of the reversible isomerization of R-glyceraldehyde 3-phosphate (GAP) to dihydroxyacetone phosphate (DHAP) by triosephosphate isomerase (TIM) from Trypanosoma brucei brucei (Tbb) has been investigated. The I172A and L232A mutations result in 100- and 6-fold decreases in k(cat)/K(m) for the isomerization reaction, respectively. The effect of the mutations on the product distributions for the catalyzed reactions of GAP and of [1-(13)C]-glycolaldehyde ([1-(13)C]-GA) in D(2)O is reported. The 40% yield of DHAP from wild-type Tbb TIM-catalyzed isomerization of GAP with intramolecular transfer of hydrogen is found to decrease to 13% and to 4%, respectively, for the reactions catalyzed by the I172A and L232A mutants. Likewise, the 13% yield of [2-(13)C]-GA from isomerization of [1-(13)C]-GA in D(2)O is found to decrease to 2% and to 1%, respectively, for the reactions catalyzed by the I172A and L232A mutants. The decrease in the yield of the product of intramolecular transfer of hydrogen is consistent with a repositioning of groups at the active site that favors transfer of the substrate-derived hydrogen to the protein or the oxygen anion of the bound intermediate. The I172A and L232A mutations result in (a) a >10-fold decrease (I172A) and a 17-fold increase (L232A) in the second-order rate constant for the TIM-catalyzed reaction of [1-(13)C]-GA in D(2)O, (b) a 170-fold decrease (I172A) and 25-fold increase (L232A) in the third-order rate constant for phosphite dianion (HPO(3)(2-)) activation of the TIM-catalyzed reaction of GA in D(2)O, and (c) a 1.5-fold decrease (I172A) and a larger 16-fold decrease (L232A) in K(d) for activation of TIM by HPO(3)(2-) in D(2)O. The effects of the I172A mutation on the kinetic parameters for the wild-type TIM-catalyzed reactions of the whole substrate and substrate pieces are consistent with a decrease in the basicity of the carboxylate side chain of Glu-167 for the mutant enzyme. The data provide striking evidence that the L232A mutation leads to a ca. 1.7 kcal/mol stabilization of a catalytically active loop-closed form of TIM (E(C)) relative to an inactive open form (E(O)).     

Molten flux synthesis of an analogous series of layered alkali samarium selenogermanate compounds

In this work, we used the molten chalcogenide flux synthetic method to form an analogous series of alkali samarium selenogermanates, with the general formula ASmGeSe(4) (A = K, Rb, Cs). Using a constant reactant stoichiometry, we relate the monoclinic KLaGeSe(4) structure type to the orthorhombic CsSmGeS(4) structure type. KSmGeSe(4) [in space group P2(1) with cell parameters a = 6.774(1) A, b = 6.994(1) A, c = 8.960(2) A, beta = 108.225(3) degrees, and V = 403.2(1) A(3) (Z = 2)], RbSmGeSe(4) [in space group P2(1)2(1)2(1) with cell parameters a = 6.7347(8) A, b = 7.0185(9) A, c = 17.723(2) A, and V = 837.7(2) A(3) (Z = 4)], and CsSmGeSe(4) [in space group P2(1)2(1)2(1) with cell parameters a = 6.707(2) A, b = 7.067(2) A, c = 18.334(6) A, and V = 869.1(5) A(3) (Z = 4)] were formed under identical synthetic conditions by changing the identity of the alkali ion from K to Rb or Cs, respectively. Additionally, with the substitution of sodium into the reaction, a triclinic structure with the approximate formula NaSmGeSe(4) was found with the cell parameters a = 6.897(2) A, b = 9.919(2) A, c = 11.183(2) A, alpha = 84.067(4) degrees, beta = 88.105(4) degrees, gamma = 73.999(4) degrees, and V = 731.5(3) A(3). In addition to single-crystal diffraction, Raman and diffuse reflectance UV-visible spectroscopic measurements have been used to characterize these compounds.     

Influence of selectivity on the supramolecular polymerization of AB-type polymers capable of Both A x A and A x B interactions

The supramolecular polymerization of two AB-type monomers capable of hydrogen-bond-mediated A x B heterocoupling and A x A homocoupling is discussed. The AB-type supramolecular polymerization is based on the strong interaction between self-dimerizing 2-ureido-pyrimidinone (UPy) and 2,7-diamido-1,8-naphthyridine (NaPy). In an effort to reduce the "self-stoppered" effect that is inherently present in these supramolecular polymerizations we used a novel ureido-pyrimidinone substituted with a dibutylamino group at the pyrimidinone ring. As a result of the substitution, the dimerization constant of the novel UPy unit is lowered compared to the previous UPy unit while the heterodimerization strength is retained. Unexpectedly, the increased selectivity toward heteroassociation not only influences the concentration-dependent degree of polymerization due to reduction of the "self-stoppered" effect but also has a pronounced effect on the ring-chain equilibrium by increasing the tendency to cyclize. In order to quantitatively explain our results, a model was developed that accurately predicts the degree of polymerization by taking into account homo- and heterodimerization as well as cyclization. Finally, molecular weight distributions for noncyclizing AB supramolecular polymerizations with and without a reversible A x A interaction are calculated. It is found that the molecular weight distribution becomes narrower when A x A interactions are present.     

A Developmental Analysis of Ecdysteroids During the Metamorphosis of Drosophila Melanogaster

Abstract

A combination of ion suppression reverse phase high pressure liquid chromatography (RP-HPLC) and differential radioimmunoassay (RIA) was used to identify and quantify ecdysteroids from Drosophila melanogaster during the development of the white puparium to the adult. The whole body ecdysteroid titer revealed a large peak approximately 30 hours after pupariation. RP-HPLC-RIA analysis of the brain-ring gland complex secretion in vitro revealed the presence of: ecdysone, 20-deoxymakisterone A, and a yet uncharacterized low polarity ecdysteroid (LP-1). The metabolism of ecdysone and 20-deoxymakisterone A was followed by analysis of the ecdysteroids during development. The white puparium (0 hour) yielded a four-fold greater quantity of free 20-hydroxyecdysone and makisterone A than ecdysone and 20-deoxymakisterone A, respectively, indicating high 20-monooxygenase activity during this stage. Another metabolite of ecdysone, 20,26-dihydroxyecdysone, was present at a quantity intermediate between that of ecdysone and 20-hydroxyecdysone. Highly polar ecdysteroids (conjugates) treated with an esterase-phosphatase mixture yielded the free ecdysteroids, ecdysone, 20-deoxymakisterone A, 20-hydroxyecdysone, and makisterone A, suggesting the presence of novel ecdysteroid conjugates of 20-deoxymakisterone A and makisterone A. At 18 hours post-pupariation the levels of all free ecdysteroids were reduced when compared to the 0 hour white puparium with the highly polar ecdysteroids predominating. By 30 hour after pupariation the level of free ecdysteroids had increased, indicating net ecdysteroid synthesis. Both ecdysone and 20-deoxymakisterone A were in greater concentrations than 20-hydroxyecdysone and makisterone A, indicating a reduced level of 20-monooxygenase activity at this stage. At 48 hours post-pupariation Drosophila contained decreasing amounts of ecdysteroids except for 20,26-dihydroxy- ecdysone and low polar products. 20, 26-Dihydroxyecdysone was the only known ecdysteroid to remain at a high level during the rest of adult development.     

High-resolution laser excitation spectroscopy of the A2E-X2A1 transition of SrCH3

High-resolution laser excitation spectroscopy has been used to record the A (2)E-X (2)A(1) electronic transition of SrCH(3) in a laser ablation/molecular jet source. Transitions arising from the K(')=1<--K(")=0, K(')=0<--K(")=1, and K(')=2<--K(")=1 subbands have been observed and assigned. The data were modeled with (2)E and (2)A(1) symmetric top Hamiltonian matrices in a Hund's case (a) basis, using a least squares fitting program. Rotational and fine structure parameters for the A (2)E state were determined. A comparison of the spin-orbit energy separation in the A (2)E state to other strontium containing free radicals showed that the Jahn-Teller effect is negligible. The spin-rotation constants for the A (2)E state were calculated using the pure precession model and were found to be in good agreement with the experimentally determined parameters. These calculations suggest that the A (2)E state of SrCH(3) is not entirely of p orbital character. The rotational constants were used to estimate the structural parameters of SrCH(3) in the A (2)E state. The strontium-carbon bond length was found to decrease by approximately 0.006 A, and the hydrogen-carbon-hydrogen bond angle opened by approximately 0.8 degrees compared to the X (2)A(1) state, similar to the geometry changes observed for CaCH(3).     

Determination of the stereochemistry of anhydroerythromycin A, the principal degradation product of the antibiotic erythromycin A

Anhydroerythromycin A arises from the acid-catalysed degradation of erythromycin A both in vitro and in vivo. It has negligible antibacterial activity, but inhibits drug oxidation in the liver, and is responsible for unwanted drug-drug interactions. Its structure has 18 chiral centres common with erythromycin A, but C-9 (the spiro carbon) is also chiral in anhydroerythromycin and its stereochemistry has not previously been reported; both 9R- and 9S-anhydroerythromycin A are plausible structures. An understanding of the chirality at C-9 was expected to throw light on the mechanism of acid-catalysed degradation of erythromycin A, a subject that has been debated in the literature over several decades.We now report a determination of the three-dimensional structure of anhydroerythromycin A, including the stereochemistry at C-9, by NMR and molecular modelling. In parallel, the relative stereochemistry of anhydroerythromycin A 2'-acetate was determined by X-ray crystallography. Both compounds were shown to have 9R stereochemistry, and anhydroerythromycin A exhibited considerable conformational flexibility in solution.     

Efficient and versatile stereoselective synthesis of cryptophycins

The cryptophycins are a family of cyclic depsipeptides with four retrosynthetic units A to D which correspond to the respective amino acids and hydroxy acids. A new synthetic route to unit A allows the selective generation of all four stereogenic centres by introducing two of them in a catalytic asymmetric dihydroxylation, followed by substrate-controlled diastereoselective reactions. The diol also serves as the epoxide precursor. This approach provides selective access to stereoisomers of unit A (enantiomers, epimers) for structure-activity relationship studies. The unit A derivatives were incorporated into cryptophycin-1, cryptophycin-52 and a novel epimer of cryptophycin-52.     

Insight into binding of calyculin A to protein phosphatase 1: isolation of hemicalyculin a and chemical transformation of calyculin A

Calyculin A isolated from the marine sponge Discodermia calyx is a potent inhibitor of protein phosphatases 1 and 2A. We attempted to elucidate its mode of binding to the enzymes by examining the activity of natural and chemically transformed derivatives. Ten natural derivatives including a new compound, hemicalyculin A, were provided. The structure of hemicalyculin A, which comprises the southern hemisphere of calyculin A, was firmly established by chemical methods. Six compounds were prepared by selective modifications of functional groups in calyculin A. The enzyme inhibitory activity of these compounds indicated that 17-phosphate, 13-hydroxyl, and the hydrophobic tetraene moieties were all necessary for binding to the enzymes. The derivatives lacking the peptide portion were less cytotoxic even when they possessed full enzyme inhibitory activity.     

Total synthesis of (+)-mycalamide A

A convergent total synthesis of (+)-mycalamide A is described. A Yb(OTf)3-TMSCl catalytic system is used to synthesize a trioxadecalin ring system, which contains the right segment of mycalamide A. In addition, a tetrahydropyran ring, which is the left segment, is constructed with use of a novel one-pot delta-lactonization protocol. Both segments are prepared from a common starting material, d-mannitol. These segments are then coupled and the functional groups are transformed to synthesize (+)-mycalamide A.     

Assignment of the absolute configuration of blasticidin A and revision of that of aflastatin A

The absolute configuration of blasticidin A, a strong inhibitor of aflatoxin production by Aspergillus parasiticus, was assigned by adding the data of relative configurations at its diol and pentaol moieties to previously known stereochemistry. Similarity of the NMR data of blasticidin A to those of aflastatin A allowed us to revise the stereochemistry of the diol and pentaol moieties of aflastatin A.     

Effect of amidoalkyl group as spacer on aggregation properties of guanidine-type surfactants

Dodecanoyl amidoalkylguanidine hydrochlorides (C(12)A(m)G, m = 2, 3, 4, 6) are cationic surfactants that have an amidoalkyl group (A(m)) as spacer between the cationic guanidine and hydrophobic groups in the molecule. The effect of the A(m) group on the aggregation properties of the surfactants was evaluated through measurements of their critical micelle concentration (cmc) value, Krafft point, phase behavior, area occupied by one molecule at the air/water interface, and micellar aggregation number. Dodecylguanidine hydrochloride (C(12)A(0)G) with no A(m) group is a unique cationic surfactant because it exhibits a strong tendency for self-assembly when compared with common ionic surfactants, due to the hydrogen bonding between its guanidine groups in addition to the hydrophobic interaction between its alkyl chains [M. Miyake, K. Yamada, N. Oyama, Langmuir 24 (2008) 8527-8532]. In contrast, C(12)A(m)G showed a decreasing tendency for self-assembly with increasing alkyl chain length, m, of the A(m) group up to m = 3, above which the tendency increased. Such changes in aggregation tendency of the surfactants were suggested to arise from an increased bulkiness of the hydrophilic part caused by the A(m) group, resulting in a decrease in the hydrogen bonding between the guanidine groups and an increase in micellization through the cooperative hydrophobic interaction between the hydrophilic groups. From the balance of these effects, the area of the hydrophilic part of C(12)A(4)G was the largest and the hydrogen bonding between the guanidine groups in C(12)A(4)G was weakened. It is suggested in guanidine-type surfactant that A(4) gave a similar aggregation tendency to traditional ionic surfactants and a weak effect for skin.