Water-splitting manganese complex controls light-induced redox changes of cytochrome <Emphasis Type="Italic">b</Emphasis><Subscript>559</Subscript> in Photosystem II

The effect of water-splitting Mn complex on light-induced redox changes of cytochrome b ₅₅₉ (cyt b ₅₅₉) was studied in spinach photosystem II (PSII) membranes. Photoreduction of the heme iron in the intact PSII membranes was completely suppressed by DCMU, whereas photoreduction and photooxidation of the heme iron in the Mn-depleted PSII membranes were unaffected by DCMU. Interesingly, photoreduction and photooxidation of the heme iron in the Mn-depleted PSII membranes were completely diminished by exogenous superoxide dismutase (SOD), whereas no effect of SOD on photoreduction of the heme iron was observed in the intact PSII membranes. The current work shows that the light-induced redox changes of cyt b ₅₅₉ proceed via a different mechanism in the both types of PSII membranes. In the intact PSII membranes, photoreduction of the heme iron is mediated by plastoquinol. However, in the Mn-depleted PSII membranes, photoreduction and photooxidation of the heme iron are mediated by superoxide anion radical formed in PSII.     

Interaction of alkyl ammonium derivatives with red cells: Hemolysis and sodium pump inhibition studies

Summary Members of four homologous series of tetra-alkyl ammonium bromides (R ₃N⁺(CH₂) _n–1·CH₃Br^– whereR=H, CH₃ or C₂H₅ andRN⁺H₃Br^– whereR represents the isomeric butyl series) have been synthesized and tested as sodium pump inhibitors, measured as ouabain-sensitive K⁺ influx, and as hemolytic agents on human red cells.Potency for both effects is presented graphically, plotting the logarithm of the concentration for half maximal effect against alkyl chain length. Both hemolysis and pump inhibition studies yielded a biphasic response consisting of two good straight lines, with effectiveness increasing up to C10–12 and then remaining constant up to C20.For hemolysis the alkyl ammonium series was most effective. The calculated free-energy change per methylene group was the same for three series of compounds, but the free-energy contribution from the headgroup was lower for the ammonium series.In contrast, although pump inhibition studies also yielded simple biphasic plots, inhibition occurred at 3- to 50-fold lower concentrations and there were significant differences between the three series, both in the free-energy changes per methylene group and in the headgroup contributions.We have analyzed these results thermodynamically to take account of hydrophobic interactions and the conformation of the alkyl chains.     

Hydrogenase-Mediated Activities in Isolated Chloroplasts of Chlamydomonas reinhardii

Isolated intact chloroplasts of Chlamydomonas reinhardii were found to catalyze photoreduction of CO₂ in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea when adapted under an atmosphere of H₂ demonstrating the association of a hydrogenase and anaerobic adaptation system with these plastids. The specific activity of photoreduction was approximately one third that detected in cells and protoplasts. Photoreduction was found to have a lower osmoticum optimum relative to aerobically maintained chloroplasts (50 millimolar versus 120 millimolar mannitol). 3-Phosphoglycerate (3-PGA) stimulated photoreduction up to a peak at 0.25 millimolar beyond which inhibition was observed. In the absence of 3-PGA, inorganic phosphate had no effect on photoreduction but in the presence of 3-PGA, inorganic phosphate also stimulated the reaction. Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone inhibited photoreduction but inhibition by the former could be partially overcome by exogenously added ATP. The intact plastid can also catalyze photoevolution of H₂ while lysed chloroplast extracts catalyzed the reduction of methyl viologen by H₂. Both reactions occurred at rates approximately one-third of those found in cells. The oxyhydrogen reaction in the presence or absence of CO₂ was not detected.     

STUDIES ON PENETRATION OF DYES WITH GLASS ELECTRODE : V. WHY DOES AZURE B PENETRATE MORE READILY THAN METHYLENE BLUE OR CRYSTAL VIOLET?

Glass electrode measurements of the pH value of the sap of cells of Nitella show that azure B in the form of free base penetrates the vacuoles and raises the pH value of the sap to about the same degree as the free base of the dye added to the sap in vitro, but the dye salt dissolved in the sap does not alter the pH value of the sap. It is concluded that the dye penetrates the vacuoles chiefly in the form of free base and not as salt. The dye from methylene blue solution containing azure B free base as impurity penetrates and accumulates in the vacuole. This dye must be azure B in the form of free base, since it raises the pH value of the sap to about the same extent as the free base of azure B dissolved in the sap in vitro. The dye absorbed by the chloroform from methylene blue solution behaves like the dye penetrating the vacuole. These results confirm those of spectrophotometric analysis previously published. Crystal violet exists only in one form between pH 5 and pH 9.2, and does not alter the pH value of the sap at the concentrations used. It does not penetrate readily unless cells are injured. A theory of "multiple partition coefficients" is described which explains the mechanism of the behavior of living cells to these dyes. When the protoplasm is squeezed into the sap, the pH value of the mixture is higher than that of the pure sap. The behavior of such a mixture to the dye is very much like that of the sap except that with azure B and methylene blue the rise in the pH value of such a mixture is not so pronounced as with sap when the dye penetrates into the vacuoles. Spectrophotometric measurements show that the dye which penetrates from methylene blue solution has a primary absorption maximum at 653 to 655 mµ (i.e., is a mixture of azure B and methylene blue, with preponderance of azure B) whether we take the sap alone or the sap plus protoplasm. These results confirm those previously obtained with spectrophotometric measurements.     

Syntheses of Jasmonic Acid Related Compounds and Their Structure-Activity Relationships on the Growth of Rice Seedings

Jasmonic acid (JA)-related compounds were synthesized, and their inhibitory activities on rice seedling growth were investigated. Three functions (C-1 CH₂COOH or CH₂COOCH₃, C-2 (Z)-2′-pentenyl or n-pentyl and C-3 ketone or hydroxyl) were essential for exhibiting inhibitory activity in this series of compounds. A dihydro-JA-related compound, 4-acetyl-nonanoic acid, also showed inhibitory activity similar to JA.     

Unusual packing of ET molecules caused by π-π stacking interactions with TRISPHAT molecules in two [ET][TRISPHAT] salts (ET = bis(ethylenedithio)tetrathiafulvalene, TRISPHAT = (tris(tetrachlorobenzenediolato)phosphate(V)))

The synthesis, structure and physical properties of two new radical salts formed with the organic donor bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF or ET) and a racemic mixture of the chiral anion (tris(tetrachlorobenzenediolato)phosphate(V)) (TRISPHAT) are reported. The structure of the salts (ET)₄[TRISPHAT]₄ · 3.5H₂O (1) and (ET)(TRISPHAT) · CH₂Cl₂ · CH₃CN (2) has been solved by X-ray single crystal diffraction. Unusual packings of ET molecules are obtained in the two structures. The electrical properties indicate that both compounds are insulators. This is in agreement with the isolation of the ET molecules and their complete ionization. On the other hand, the anisotropy of the ESR lines has been studied by Q-band ESR spectra.     

ON THE NATURE OF THE DYE PENETRATING THE VACUOLE OF VALONIA FROM SOLUTIONS OF METHYLENE BLUE

When uninjured cells of Valonia are placed in methylene blue dissolved in sea water it is found, after 1 to 3 hours, that at pH 5.5 practically no dye penetrates, while at pH 9.5 more enters the vacuole. As the cells become injured more dye enters at pH 5.5, as well as at pH 9.5. No dye in reduced form is found in the sap of uninjured cells exposed from 1 to 3 hours to methylene blue in sea water at both pH values. When uninjured cells are placed in azure B solution, the rate of penetration of dye into the vacuole is found to increase with the rise in the pH value of the external dye solution. The partition coefficient of the dye between chloroform and sea water is higher at pH 9.5 than at pH 5.5 with both methylene blue and azure B. The color of the dye in chloroform absorbed from methylene blue or from azure B in sea water at pH 5.5 is blue, while it is reddish purple when absorbed from methylene blue and azure B at pH 9.5. Dry salt of methylene blue and azure B dissolved in chloroform appears blue. It is shown that chiefly azure B in form of free base is absorbed by chloroform from methylene blue or azure B dissolved in sea water at pH 9.5, but possibly a mixture of methylene blue and azure B in form of salt is absorbed from methylene blue at pH 5.5, and azure B in form of salt is absorbed from azure B in sea water at pH 5.5. Spectrophotometric analysis of the dye shows the following facts. 1. The dye which is absorbed by the cell wall from methylene blue solution is found to be chiefly methylene blue. 2. The dye which has penetrated from methylene blue solution into the vacuole of uninjured cells is found to be azure B or trimethyl thionine, a small amount of which may be present in a solution of methylene blue especially at a high pH value. 3. The dye which has penetrated from methylene blue solution into the vacuole of injured cells is either methylene blue or a mixture of methylene blue and azure B. 4. The dye which is absorbed by chloroform from methylene blue dissolved in sea water is also found to be azure B, when the pH value of the sea water is at 9.5, but it consists of azure B and to a less extent of methylene blue when the pH value is at 5.5. 5. Methylene blue employed for these experiments, when dissolved in sea water, in sap of Valonia, or in artificial sap, gives absorption maxima characteristic of methylene blue. Azure B found in the sap collected from the vacuole cannot be due to the transformation of methylene blue into this dye after methylene blue has penetrated into the vacuole from the external solution because no such transformation detectable by this method is found to take place within 3 hours after dissolving methylene blue in the sap of Valonia. These experiments indicate that the penetration of dye into the vacuole from methylene blue solution represents a diffusion of azure B in the form of free base. This result agrees with the theory that a basic dye penetrates the vacuole of living cells chiefly in the form of free base and only very slightly in the form of salt. But as soon as the cells are injured the methylene blue (in form of salt) enters the vacuole. It is suggested that these experiments do not show that methylene blue does not enter the protoplasm, but they point out the danger of basing any theoretical conclusion as to permeability on oxidation-reduction potential of living cells from experiments made or the penetration of dye from methylene blue solution into the vacuole, without determining the nature of the dye inside and outside the cell.     

Ferredoxin-Dependent Photoreduction of the Monodehydroascorbate Radical in Spinach Thylakoids

Thylakoid-bound and stromal ascorbate peroxidases scavenge thehydrogen peroxide that is photoproduced in PSI of chloroplastthylakoids. The primary oxidation product of ascorbate in thereaction catalyzed by ascorbate peroxidase, the monodehydroascorbate(MDA) radical, is photoreduced by thylakoids [Miyake and Asada(1992) Plant Cell Physiol. 33: 541]. We have now shown thatthe photoreduction of MDA radical in spinach thylakoids is largelydependent on ferredoxin (Fd), as determined by the monitoringthe MDA radical by electron paramagnetic resonance. Further,the reduced Fd generated by NADPH and Fd-NADP reductase couldreduce the MDA radical at a rate of over 10⁶ M^–1 s^–1,indicating that the photoreduced Fd in PSI directly reducesthe MDA radical to ascorbate. Photoreduction of NADP⁺ by spinach thylakoids was suppressedby the MDA radical and conversely that of MDA radical was suppressedby NADP⁺, indicating a competition between the MDA radical andNADP⁺ for the photoreduced Fd in PSI. The ratio of the rateconstant for the photoreduction of MDA radical to that for thephotoreduction of NADP⁺ was estimated to be more than 30 to1. Thus, MDA radical is preferentially photoreduced as comparedto NADP⁺. From these results, we propose that the thylakoid-boundascorbate peroxidase and the Fd-dependent photoreduction ofMDA radical in PSI are the primary system for the scavengingof the hydrogen peroxide that is photoproduced in the thylakoids. (Received December 9, 1993; Accepted February 16, 1994)     

Metachromasia of basic dyes induced by mercuric chloride. I

Summary Interactions of the cationic dye methylene blue with mercuric chloride have been studied conductometrically, analytically and spectrophotometrically. Methylene blue produces red colored precipitate with mercuric chloride; in presence of large excess of mercuric chloride a strong metachromasia is induced in the dye. Metachromasia induced by mercuric chloride is more hypsochromic as well as hypochromic than that induced by chromotopes like heparin. The complexes formed between methylene blue and mercuric chloride have variable compositions, the complex responsible for the red metachromatic color of the dye has the composition 2 dye: 1 HgCl₂. A model has been proposed for the metachromatic complex consisting hexa-coordinated mercury, dye is coordinated to the mercury by donating the lone pair electrons of terminal nitrogen. The non-metachromatic dye capri blue also interacts with mercuric chloride but without any change in the visible spectrum. Potassium iodide also gives metachromatic reddish blue colored precipitate with methylene blue.University Research Scholar.     

Synthesis, spectroscopic properties, X-ray single crystal analysis and antimicrobial activities of organotin(IV) 4-(4-methoxyphenyl)piperazine-1-carbodithioates

A series of mononuclear organotin(IV) complexes of the types, R₃SnL {R = C₄H₉ (1), C₆H₁₁ (2), CH₃ (3) and C₆H₅ (4)}, R₂SnClL {R = C₄H₉ (5), C₂H₅ (7) and CH₃ (9)} and R₂SnL₂ {R = C₄H₉ (6), C₂H₅ (8) and CH₃ (10)}, have been synthesized, where L = 4-(4-methoxyphenyl)piperazine-1-carbodithioate. The ligand-salt and the complexes have been characterized by Raman, FT-IR and multinuclear NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy and elemental microanalysis (CHNS). The spectroscopic data substantiate coordination of the ligands to the organotin moieties. The structures of complexes 4 and 6 have been determined by single-crystal X-ray diffraction and illustrate the asymmetric bidentate bonding of the ligand. The packing diagrams indicate O···H and π···H intermolecular interactions in complex 4 and intermolecular S₂C···H interactions in complex 6, resulting in layer structures for both complexes. A subsequent antimicrobial study indicates that the compounds are active biologically and may well be the basis for a new class of fungicides.     

Incorporation of diacids into the polyglycine II structure: Model studies

Aliphatic diacids Eare often incorporated into polypeptide structures in order to obtain model compounds for hormones, protein turns, etc. They are also fundamental components of many commercial polyamides. On the other hand glycine, the simplest amino acid, shows unique conformational features. In order to better understand the structure of such compounds, we have synthetized and determined the molecular structure of three models represented by the general formula CH₃-CH₂CH₂-NH-CO-CH₂NH-CO-(CH₂)_n-2-CO-NH-CH₂CO-NH-CH₂CH₂CH₃, with n = 3, 4, or 6. Conformational differences have been found in the dicarboxylic moiety, whereas glycine always has the polyglycine II conformation. The -CO-(CH₂)_n-2-CO- segment adopts a folded conjformation: SS, TGT, and S?TGS? for n = 3, 4, and 6, respectively. Molecular packing is always pseiidohexagonal and a network of hydrogen bonds oriented in three directions at 120° is formed. The results are of interest in order to provide information about polyamides in which gljrine residues are incorporated. Our results confirm the tendency of glycine residues to adopt the polyglycine II conformation in its copolymers with aliphatic compounds. © 1995 John Wiley & Sons, Inc.     

On the appearance and role of a spacer group in the protein amino acids

Summary Of the 20 protein amino acids, 16 have a methylene group at the position, and a further three bear a methine group. No aromatic, carboxamido, carboxylic carbon, or hetero atoms are attached directly to the carbon, but they are separated by this methylene or occasionally by a longern-alkylene spacer group. Therefore, the structure of the protein amino acids should rather be formulated as H₂N–CH((CH₂)_n–R)–COOH instead of the generally accepted H₂N–CH(R)–COOH. The appearance of and the role played by the spacer group are discussed in an evolutionary context. It is suggested that the spacer group appeared as a result of prebiotic selection, based on the relative abundance, racemization rate, and suitability for thermal polymerization of the protein amino acids and their homologs with various spacer group lengths. At the biotic level of evolution the requirements for ribosomal polymerization, as well as the abilities of polypeptides to maintain a stable and flexible threedimensional structure and to bind ligands are considered and are proposed to have been responsible for the possible exclusion of longer spacer groups. It is concluded that the general role of the spacer group is to ensure the uniformity of the constant regions H₂N–CH(-)–COOH and the individuality of the R contact groups by spatially separating them.     

Light-induced fluorescence changes in<Emphasis Type="Italic"> Phycomyces</Emphasis>: evidence for blue light-receptor associated flavo-semiquinones

Light-induced fluorescence changes (LIFCs) were detected in sporangiophores of the blue-light-sensitive fungus Phycomyces blakesleeanus (Burgeff). The LIFCs can be utilized as a spectrophotometric assay for blue-light photoreceptors and for the in vivo characterization of their photochemical primary reactions. Blue-light irradiation of sporangiophores elicited a transient decrease and subsequent regeneration of flavin-like fluorescence emission at 525 nm. The signals recovered in darkness in about 120 min. In contrast to blue light, near-UV (370 nm) caused an increase in the fluorescence emission at 525 nm. Because the LIFCs were altered in a light-insensitive madC mutant with a defective photoreceptor, the fluorescence changes must be associated with early photochemical events of the transduction chain. Action spectra for the fluorescence changes at 525 nm showed major peaks near 470 and 600 nm. Double-pulse experiments involving two consecutive pulses of either blue and near-UV, blue and red, or near-UV and red showed that the responses depended on the sequence in which the different wavelengths were applied. The results indicate a blue-light receptor with intermediates in the near-UV, blue and red spectral regions. We explain the results in the framework of a general model, in which the three redox states of the flavin photoreceptor, the oxidized flavin (Fl), the flavo-semiquinone (FlH^·), and the flavo-hydroquinone (FlH₂) are each acting as chromophores with their own characteristic photochemical primary reactions. These consist of the photoreduction of the oxidized flavin generating semiquinone, the photoreduction of the semiquinone generating hydroquinone, and the photooxidation of the flavo-hydroquinone regenerating the pool of oxidized flavins. The proposed mechanism represents a photocycle in which two antagonistic photoreceptor forms, Fl and FlH₂, determine the pool size of the biological effector molecule, the flavo-semiquinone. The redox changes that are associated with the photocycle are maintained by redox partners, pterins, that function in the near-UV as secondary chromophores.Abbreviations FAD flavin adenine dinucleotide - Fl oxidized flavin - FlH flavo-semiquinone radical - FlH₂ flavo-hydroquinone - LIAC light-induced absorbance change - LIFC light-induced fluorescence change - Pt oxidized pterin - PtH₂ dihydro-pterin - PtH₄ tetrahydro-pterin     

Chemical evolution of dehydrogenases: Amino acid pentacyanoferrate (II) as possible intermediates

Dehydrogenation of ascorbic acid and reduced nicotinamide adenine dinucleotide (NADH) with methylene blue using complexes of the type [Fe(II)(CN)₅ (L)] ^n– (wheren=3 or 4; L=glycine, histidine, imidazole, and triglycine) as catalyst have been studied at pH 9.18. Similar kinetic behavior was observed for the dehydrogenation of ascorbic acid as well as for NADH; both reactions showed first order dependency on the substrates. First order dependence was observed only at lower concentrations of methylene blue; at higher concentrations of methylene blue, the reactions were independent of methylene blue. The order with respect to catalyst varied between 0.3–0.5. A tentative mechanism which conforms to the observed kinetics has been proposed. It is believed that on the primitive earth when the reducing potential of the atmosphere was not high enough, lower oxidation state iron complexes like [Fe(II)(CN)₅(L)] ^n– might have been involved in dehydrogenase-type activity.     

Studies on electron transport associated with Photosystem I. I. Functional site of plastocyanin: Inhibitory effects of HgCl2 on electron transport and plastocyanin in chloroplasts

1. Incubation of chloroplasts with HgCl₂ at a molar ratio of HgCl₂ to chlorophyll of about unity, induced a complete inhibition of the methyl viologen Hill reaction, as well as methyl viologen photoreduction with reduced 2,6-dichlorophenolindophenol (DCIP) as electron donor. Photooxidation of cytochrome ? was similarly sensitive towards HgCl₂, whereas photooxidation of P700 was resistant to the poison. Photoreduction of cytochrome ? and light-induced increase in fluorescence yield were enhanced by the HgCl₂ treatment of chloroplasts.     

New ways of determining structural groups in brown coals and their bioconversion products by FT IR spectroscopy

New methods of determining the structural groups —COOH and —CH₂— have been developed. The investigation of carboxyl groups is possible both after derivatization with p-fluorophenacylbromide and by quantitative interpretation of the Fourier transform infrared (FT IR) spectra. There exists a linear relationship between the results of these two methods that is generally valid for the analysis of all brown coal components. The maximum extinction coefficient of the symmetric stretching vibration band of the CH₂ groups has been determined using model substances. This allows quantification of this structural group directly from the FT IR spectrum. The results agree with the contents of methylene groups as determined by ¹³C-cross polarization–magic angle spinning–nuclear magnetic resonance (¹³C CPMAS NMR) spectroscopy. Using these methods, the COOH and CH₂ groups contained in brown coals of the North Rhine region and in their bioconversion products have been quantified. Received: 21 December 1999 / Received revision: 25 April 2000 / Accepted: 1 May 2000     

FURTHER STUDIES ON THE INHIBITION OF CYPRIDINA LUMINESCENCE BY LIGHT,WITH SOME OBSERVATIONS ON METHYLENE BLUE

1. Eosin, erythrosin, rose bengale, cyanosin, acridine, and methylene blue act photodynamically on the luminescence of a Cypridina luciferin-luciferase solution. In presence of these dyes inhibition of luminescence, which without the dye occurs only in blue-violet light, takes place in green, yellow, orange, or red light, depending on the position of the absorption bands of the dye. 2. Inhibition of Cypridina luminescence without photosensitive dye in blue-violet light, or with photosensitive dye in longer wave-lengths, does not occur in absence of oxygen. Light acts by accelerating the oxidation of luciferin without luminescence. Eosin or methylene blue act by making longer wave-lengths effective, but there is no evidence that these dyes become reduced in the process. 3. The luciferin-oxyluciferin system is similar to the methylene white-methylene blue system in many ways but not exactly similar in respect to photochemical change. Oxidation of the dye is favored in acid solution, reduction in alkaline solution. However, oxidation of luciferin is favored in all pH ranges from 4 to 10 but is much more rapid in alkaline solution, either in light or darkness. There is no evidence that reduction of oxyluciferin is favored in alkaline solution. Clark''s observation that oxidation (blueing) of methylene white occurs in complete absence of oxygen has been confirmed for acid solutions. I observed no blueing in light in alkaline solution.     

Photoreactions of cytochrome b6 in systems using resolved chloroplast electron-transfer complexes

Photoreactions of cytochrome b₆ have been studied using resolved chloroplast electron-transfer complexes. In the presence of Photosystem (PS) II and the cytochrome b₆-f complex, photoreduction of the cytochrome can be observed. No soluble components are required for this reaction. Cytochrome b₆ photoreduction was found to be inhibited by quinone analogs, which inhibit at the Rieske iron-sulfur center of the cytochrome complex, by the addition of ascorbate and by depletion of the Rieske center and bound plastoquinone from the cytochrome complex. Photoreduction of cytochrome b₆ can also be demonstrated in the presence of the cytochrome complex and PS I. This photoreduction requires plastocyanin and a low-potential electron donor, such as durohydroquinone. Cytochrome b₆ photoreduction in the presence of PS I is inhibited by quinone analogs which interact with the Rieske iron-sulfur center. These results are discussed in terms of a Q-cycle mechanism in which plastosemiquinone serves as the reductant for cytochrome b₆ via an oxidant-induced reductive pathway.     

Study of structure-activity relationship among similar analogues of GSB-106, a dipeptide mimetic of a brain-derived neurotrophic factor

In the previous work, we synthesized a dimeric dipeptide mimetic of the 4th loop of BDNF, i.e., hexamethylenediamide bis(N-monosuccinil-L-seryl-L-lysine) (GSB-106), which has neuroprotective activity in vitro in a concentration range of 10^?5–10^?8 M and antidepressant activity in vivo at intraperitoneal doses of 0.1 and 1 mg/kg in rats. We studied the structural and functional relationships among analogues of GSB-106. A glycine scan was performed, and a number of corresponding compounds were synthesized: GT-105 (where lysine was replaced by glycine), GT-107 (where serine was replaced by glycine), and GT-106Ac (where the monosuccinic radical was replaced by the acetyl group). We studied the dependence of the activity on the configuration of amino acid residues in the following compounds: GT-107D (D-enantiomer of GT-107), GT-106DL (L-serine was replaced by D-serine), GT-106LD (L-lysine was replaced by D-lysine). The investigation of these compounds in the HT22 cell culture in conditions of oxidative stress showed that only two analogues of GSB-106 had the neuroprotective effect, i.e., in the case of the replacement of serine by glycine and the succinic radical by the acetic group. This effect disappeared when the lysine residue was replaced by glycine or D-lysine and the L-serine residue, by D-serine. The results indicate the key role of the lysine side group in GSB-106 for its neuroprotective activity. The L-configuration is necessary for both the lysine and serine residues. The configuration of the lysine residue remains critical in the absence of the serine side group. Thus, the minimum neuroprotective pharmacophore of the beta-turn of the 4th loop of BDNF is the following fragment: HOOC-CH₂-CH₂-CO-NH-(S)CH(CH2OH)-CO-NH-(S)CH((CH₂)₄NH₂)-CO-NH-(CH₂)₃ Only GT-106Ac out of two analogues of GSB-106 having the neuroprotective activity showed the antidepressant activity. This indicates more stringent structural requirements for the manifestation of the antidepressant activity. The results can be useful for designing new active mimetics of BDNF.