Guanidyl Groups Research Articles

Effective Enrichment of Phosphopeptides Using Magnetic Polyoxometalate-Based Metal-Organic Frameworks.

In this study, magnetic polyoxometalate-based metal-organic frameworks (Fe3O4-POMOFs) were designed and applied to the enrichment of phosphopeptides. Thanks to the abundant metal oxide and metal ion sites, the material had a strong affinity for phosphopeptides. Simultaneously, the high amount of amino and guanidyl groups provided hydrophilicity and positive charge for phosphopeptide capture. By coupling with MS detection, the established platform possessed good reusability, high sensitivity (0.01 fmol), and high selectivity (α-casein/β-casein/bovine serum albumin = 1:1:5000). Furthermore, the method was successfully used for the detection of phosphopeptides in nonfat milk, human serum, saliva, and A549 cell lysate, showing great potential for practical application.

Guanylation of NH2-MIL-125 under green condition: An approach to strengthen basic sites of NH2-functionalized materials for enhanced base catalysis

The NH2-MIL-125, an amine functionalized metal-organic framework, possesses good amount and strength of basic sites due to –NH2 groups, and exhibits significant activity for base catalyzed Claisen-Schmidt condensation of acetophenone and benzaldehyde to synthesize chalcone under solvent free condition. In order to further enhance the basicity and catalytic activity of NH2-MIL-125, the material was modified by the guanylation reaction. The guanylation of NH2-MIL-125 using an aqueous solution of cyanamide at room temperature (30 °C) converted some of –NH2 groups into guanidyl functionalities (16% modification) without affecting the framework structure. The guanidyl groups in the resulted material act as strong basic sites producing a stronger solid base catalyst than NH2-MIL-125. The modified NH2-MIL-125 exhibited enhanced catalytic activity for solvent free Claisen-Schmidt condensation reaction. The study shows that NH2-MIL-125 and its modified form (having guanidyl groups) are potential solid base catalysts. The developed protocol for guanylation could also be useful for the modification of amine functionalized materials under green condition to strengthen their surface basic sites for enhanced catalytic performance.

Stimuli-responsive triplet-triplet annihilation upconversion with guanidyl functionalized annihilators for enhanced ratiometric sensing of trace water in MeOH

Adding stimuli-responsiveness to TTA-UC is appealing as it provides a unique platform for biosensing and chemosensing. Here, we synthesized three guanidyl functionalized annihilators A-1∼A-3 for stimuli-responsive TTA-UC. The annihilator A-1 self-assembled into microparticles in aprotic solvent like THF, CHCl3 and toluene with the DPA units arranged in an ordered manner via the strong hydrogen bonding interactions between the guanidyl groups, which guaranteed effective energy migration of triplet excitons, thus, efficient TTA-UC with ΦUC of 10.2% was observed in THF. While MeOH degraded the well-aligned aggregates, accompanied by the decrease of ΦUC to 2.9%. For A-2 and A-3, weak UC emissions in all the investigated solvents were observed due to π-π stacking of anthracene core. Interestingly, the destroyed hydrogen-bonding network of A-1 was successfully reconstructed by the addition of trace water with ΦUC recovered from 2.9% to 9.2% when 3% water was added. We also found that the well-aligned aggregates significantly accelerated the TTA process but have no impact on the TTET process, thus, enhanced ratiometric sensing of trace H2O in methanol was achieved with the unchanged phosphorescence as the internal standard and a detection limit as low as 0.084% (v/v) was achieved.

Epitaxial Growth of Guanidyl-Functionalized Magnetic Metal-Organic Frameworks with Multiaffinity Sites for Selective Capture of Global Phosphopeptides.

The flexible and controlled synthesis of metal-organic framework (MOF)-derived hybrid nanostructures is of great significance in fine tuning of their enrichment performance in large-scale and in-depth phosphoproteome analysis. Herein, a magnetic guanidyl-functionalized MOF hybrid coating with multiaffinity sites, denoted as Fe3O4@G-ZIF-8, was fast fabricated via a one-pot epitaxial growth strategy for the first time and applied for selective and highly efficient enrichment of global phosphopeptides. The intrinsic unsaturated metal sites of ZIF-8 endow the surface-mounted MOF coatings with immobilized metal ion affinity chromatography interaction with multiphosphorylated peptides. The oriented anchoring of bifunctional guanidineacetic acid on the magnetic MOF nanospheres provides additional affinity sites (guanidyl groups) for specific recognition of phosphopeptides by "salt bridge" interaction, as well as active site carboxyl groups for the coordination with the metal ions. The as-prepared Fe3O4@G-ZIF-8 exhibits large surface area (382.5 m2 g-1), good superparamagnetic property (41.6 emu g-1) and stability, and size-exclusion effect (1.73 nm), which can serve as a specific adsorbent for global phosphopeptide analysis with satisfactory selectivity, great detection sensitivity (1 fmol), and rapid magnetic separation. Moreover, the successful application of Fe3O4@G-ZIF-8 for selective capture of both multi- and mono-phosphopeptides from human saliva and serum demonstrated the great potential of magnetic surface-mounted MOF coatings in effective identification of low-abundance phosphopeptides by matrix-assisted laser desorption ionization time-of-flight mass spectrometry from complicated biological matrices.

A concise SAR-analysis of antimicrobial cationic amphipathic barbiturates for an improved activity-toxicity profile

An amphipathic barbiturate mimic of the marine eusynstyelamides is reported as a promising class of antimicrobial agents. We hereby report a detailed analysis of the structure-activity relationship for cationic amphipathic N,N′-dialkylated-5,5-disubstituted barbiturates. The influence of various cationic groups, hydrocarbon linkers and lipophilic side chains on the compounds’ antimicrobial potency and haemolytic activity was studied. A comprehensive library of 58 compounds was prepared using a concise synthetic strategy. We found cationic amine and guanidyl groups to yield the highest broad-spectrum activity and cationic trimethylated quaternary amine groups to exert narrow-spectrum activity against Gram-positive bacteria. n-Propyl hydrocarbon linkers proved to be the best compromise between potency and haemolytic activity. The combination of two different lipophilic side chains allowed for further fine-tuning of the biological properties. Using these insights, we were able to prepare both, the potent narrow-spectrum barbiturate 8a and the broad-spectrum barbiturates 11lG, 13jA and 13jG, all having low or no haemolytic activity. The guanidine derivative 11lG demonstrated a strong membrane disrupting effect in luciferase-based assays. We believe that these results may be valuable in further development of antimicrobial lead structures.

Synthesizing N-[4-morpholinecarboximidamidoyl]carboximidamidoylated graphene oxide for fabricating high-sensitive humidity sensors

A lot of humidity sensors cannot accurately measure humidity of air containing NH3 gas due to reaction of NH3 gas with sensor materials. A guanidyl group is a strong hydrophilic group, moreover, guanidyl groups do not adsorb NH3 molecules via hydrogen or chemical bonds. In this paper, moroxydine moieties were grafted on surfaces of graphene oxide (GO) materials to synthesize N-[4-morpholinecarboximidamidoyl]carboximidamidoylated graphene oxide (MCGO) for fabricating humidity sensors. When RH increased from 11% to 95%, impedance value of the sensor decreased from 5.41 × 108 to 2.25 × 104 Ω at testing frequency 100 Hz. The change of impedance was much higher than that fabricated by GO. The sensors also exhibited short response/recovery time (2 s/20 s). Their good humidity sensing properties would be attributed to the fact that those N atoms in guanidyl groups at moroxydine moieties on the surfaces MCGO may strong interact with H atom in H2O molecules to form intermolecular hydrogen bonds and generate OH− ions to increase ionic conductivities. The impedance change of the humidity sensor at a low or high relative humidity was due to electronic or ionic conductivities, respectively.

Guanidyl-implanted UiO-66 as an efficient catalyst for the enhanced conversion of carbon dioxide into cyclic carbonates.

The development of heterogeneous catalysts for promoting epoxide cycloaddition with carbon dioxide is highly desirable for recycling CO2 and achieving the goal of carbon neutrality. Herein, we designed and synthesized Zr-based metal organic frameworks (MOFs) by implanting functional guanidyl into the framework via mixing different molar ratios of 4-guanidinobenzoic acid (Gua) with 1,4-benzenedicarboxylic acid (BDC). Consequently, a small sized Zr-MOF (∼350 nm) can be prepared by implanting Gua with 20% molar ligands, denoted as UiO-66-Gua0.2(s). Compared to large sized and different guanidyl Zr-MOFs, UiO-66-Gua0.2(s) exhibited an optimal activity on catalyzing epoxide cycloaddition with CO2 in the presence of the Bu4NBr cocatalyst. A yield of 97% for the product of chloropropene carbonate was achieved at 90 °C under 1 atm CO2. The great performance of UiO-66-Gua0.2(s) might be attributed to the synergistic effect of guanidyl groups as hydrogen-bond donors and Zr centers acting as Lewis-acidic sites. In addition, the heterogeneous catalyst of UiO-66-Gua0.2(s) exhibited a great versatility towards converting other epoxides and a satisfactory recyclability for five consecutive runs. Moreover, a plausible reaction mechanism has been proposed for UiO-66-Gua0.2(s) in promoting CO2 epoxide cycloaddition reactions.

Quantum chemical approach (DFT) of the binary complexation of Hg(II) with L-canavanine and L-arginine.

The experimental study of the complexation of the two amino acids, L-canavanine, and L-arginine, with the mercuric ion Hg(II), was completed by the characterization by a quantum calculation based on the DFT method. This study covers electronic, energetic, and structural aspects in the neutral, deprotonated, and complexed states. The atomic net charges show that the active sites of the carboxyl, guanidyl, and amino groups are the oxygen and nitrogen atoms. In fact, the L-canavanine (Can) gave stable mercuric bidentate chelates via the amino and guanidyl groups. Hg(Can)(H 2 O) 2 , Hg(Can) 2 and Hg(OH)(H 2 O)(Can), while the L-arginine (Arg) resulted in engagement of carboxyl and amino groups to bidentate complexes: Hg(Arg)(H 2 O) 2 , Hg(Arg) 2 , Hg(Arg)(OH)(H 2 O). The metal-ligand coordination bond is more rigid with the guanidyl and carboxyl groups than with the amino group; and the bond formed with the amino group is more rigid in the L-canavanine than L-arginine.

Conjugate of Thiol and Guanidyl Units with Oligoethylene Glycol Linkage for Manipulation of Oxidative Protein Folding.

Oxidative protein folding is a biological process to obtain a native conformation of a protein through disulfide-bond formation between cysteine residues. In a cell, disulfide-catalysts such as protein disulfide isomerase promote the oxidative protein folding. Inspired by the active sites of the disulfide-catalysts, synthetic redox-active thiol compounds have been developed, which have shown significant promotion of the folding processes. In our previous study, coupling effects of a thiol group and guanidyl unit on the folding promotion were reported. Herein, we investigated the influences of a spacer between the thiol group and guanidyl unit. A conjugate between thiol and guanidyl units with a diethylene glycol spacer (GdnDEG-SH) showed lower folding promotion effect compared to the thiol–guanidyl conjugate without the spacer (GdnSH). Lower acidity and a more reductive property of the thiol group of GdnDEG-SH compared to those of GdnSH likely resulted in the reduced efficiency of the folding promotion. Thus, the spacer between the thiol and guanidyl groups is critical for the promotion of oxidative protein folding.

Glycocyamine functionalized magnetic layered double hydroxides with multiple affinity sites for trace phosphopeptides enrichment

Efficient enrichment and identification of phosphopeptides are of great significance in biological applications. Glycocyamine functionalized magnetic layered double hydroxides (Fe3O4@LDH@NH2-GAA) was fabricated through an easy process. The magnetic composite possessed high surface area, good biocompatibility, and fast magnetic response. Fe3O4@LDH@NH2-GAA, combining not only metal ions (Cu2+ and Ga3+) in LDH but also functional guanidyl groups in glycocyamine, offered multiple affinity sites for phosphopeptides enrichment. With these favorable characters, it exhibited high selectivity (β-casein: bovine serum albumin = 1:5000), low detection limit (0.1 fmol), satisfactory enrichment recovery (94.5%), high adsorption capacity (82.4 mg g−1), and good repetitiveness. Moreover, the efficient enrichment of phosphopeptides by Fe3O4@LDH@NH2-GAA from nonfat milk, human saliva, serum, and A549 cell lysates further confirmed its great potential for trace biological detection and proteomic analysis.

Design of guanidyl-functionalized magnetic covalent organic framework for highly selective capture of endogenous phosphopeptides

The identification and analysis of endogenous phosphopeptides is still a scientific challenge due to their low abundance and the complicated matrix of bio-samples. Hence, the highly effective enrichment of endogenous phosphopeptides is a prerequisite for comprehensive phosphoproteome analysis. Here, a novel guanidyl-functionalized magnetic covalent organic framework (denoted as SPIO@COF-Guanidyl) nanosphere was designed for selective and efficient phosphopeptide enrichment. The SPIO@COF-Guanidyl nanospheres possessed specific recognition sites of functional guanidyl groups, large surface area, regular mesoporous structure, and superior magnetic responsiveness, resulting in excellent performances in phosphopeptide enrichment with high selectivity (β-casein/BSA = 1:1000), extremely high sensitivity (5 × 10−11 M), an excellent size-exclusion effect (β-casein digests/β-casein/bovine serum albumin (BSA) = 1:500:500), and good reusability (at least 5 times). In addition, due to the synergistic effect of functional molecules and the size-selection effect of the COF structure, SPIO@COF-Guanidyl nanospheres captured 63 unique endogenous phosphopeptides from a 10 μL sample of human saliva. Therefore, SPIO@COF-Guanidyl nanospheres possess a huge potential for trace biological detection and endogenous phosphopeptide analysis.

Facile synthesis of guanidyl-based magnetic ionic covalent organic framework composites for selective enrichment of phosphopeptides

Protein phosphorylation plays vital roles in the regulation of various biological processes involving in protein folding, molecular recognition, cell growth, and metabolism. It is prerequisite to develop effective enrichment methods of trace phosphopeptides before mass spectrometry (MS) analysis. In this study, we proposed a facile strategy to synthesize magnetic ionic covalent organic frameworks (Fe3O4@iCOFs) for the capture of phosphopeptides with guanidyl as the ionic ligand instead of the post-synthetic functionalization strategy. The developed Fe3O4@iCOFs contain a large amount of amino groups, positive charge, as well as owned superparamagnetism. The enrichment of phosphopeptides is based on the electrostatic interaction and hydrogen bonds formed between phosphate groups and guanidyl groups. By combing with MS determinations, high sensitivity of phosphopeptides (the lowest detection amount being 0.4 fmol) was achieved. The obtained material provided selective enrichment capacity of phosphopeptides from non-fat milk digest and HeLa cells, showing great potential in the detection of low-abundance phosphopeptides in complex real samples.

A Novel Cyclic Polysiloxane Linked by Guanidyl Groups Used as Flame Retardant and Antimicrobial Agent on Cotton Fabrics

A novel flame retardant and antibacterial agent, (tetramethylcyclosiloxyl-piperazin) tetra guanidine (GNCTSi) used for cotton fabrics was successfully synthesized. The limiting oxygen index (LOI) value of cotton fabric treated with 250 g/l GNCTSi reached to 30.1 %. The vertical burning test results showed that the char length of the treated cotton fabric was 6.5 cm and have no after-flame and no after-glow. Compared with untreated cotton fabric, the treated cotton fabric showed better flame retardancy and higher residue rate by themogravimetric analysis (TG). The GNCTSi exists on the treated cotton fabric was observed and the residues of cotton fabric after combustion had a homogeneous surface without break by scanning electron microscopy (SEM). The treated cotton fabric showed good antibacterial activity against E. coli and S. aureus and the inhibition zone were 2.5 mm and 2.3 mm, respectively. After repeated washing, the LOI of cotton fabric is still higher than 26 %.

Guanidyl-functionalized graphene/polysulfone mixed matrix ultrafiltration membrane with superior permselective, antifouling and antibacterial properties for water treatment

Mixed matrix membranes blended with graphene-based nanomaterials have great potential in water and wastewater treatment on account of their multiple functionalities. To solve the complicated biofouling problem and diversify the applications of membranes, novel synergistic antibacterial guanidyl-functionalized graphene/polysulfone (GFG/PSF) mixed matrix ultrafiltration membranes were prepared by a non-solvent induced phase separation method. The guanidyl-functionalized graphene nanosheets were achieved by a two-step grafting process consisting of amination and guanidination and exhibited high dispersibility in the casting solution, which showed good compatibility with the polymer matrix. Besides the advantages of partially reduced graphene oxide (GO) nanosheets in creating a stronger interaction with the bacterial cell membrane to destroy the bacteria, the induced bidendate binding between guanidyl groups and phosphate groups on the cell wall can make high sterilization rate even at low concentrations. Different techniques including XRD, FTIR, XPS, SEM, TEM, EDX, contact angle meter, filtration and antibacterial experiments were employed to characterize and investigate the performance of nanosheets and membranes. Compared with pure PSF membrane, the GFG/PSF mixed matrix membranes not only exhibited superior permeability and prominent antifouling property performance toward bovine serum albumin (BSA), but also displayed excellent antimicrobial activity and long-term duration toward Escherichia coli and Staphylococcus aureus.

N-Guanidyl and C-Tetrazole Leu-Enkephalin Derivatives: Efficient Mu and Delta Opioid Receptor Agonists with Improved Pharmacological Properties.

Leu-enkephalin and d-Ala2-Leu-enkephalin were modified at their N- and C-termini with guanidyl and tetrazole groups. The resulting molecules were prepared in solution or by solid phase peptide synthesis. The affinity of the different analogues at mu (MOP) and delta opioid receptors (DOP) was then assessed by competitive binding in stably transfected DOP and MOP HEK293 cells. Inhibition of cAMP production and recruitment of β-arrestin were also investigated. Finally, lipophilicity (logD7.4) and plasma stability of each compound were measured. Compared to the native ligands, we found that the replacement of the terminal carboxylate by a tetrazole slightly decreased both the affinity at mu and delta opioid receptors as well as the half-life. By contrast, replacing the ammonium at the N-terminus with a guanidyl significantly improved the affinity, the potency, as well as the lipophilicity and the stability of the resulting peptides. Replacing the glycine residue with a d-alanine in position 2 consistently improved the potency as well as the stability of the analogues. The best peptidomimetic of the whole series, guanidyl-Tyr-d-Ala-Gly-Phe-Leu-tetrazole, displayed sub-nanomolar affinity and an increased lipophilicity. Moreover, it proved to be stable in plasma for up to 24 h, suggesting that the modifications are protecting the compound against protease degradation.

A Combination of Guanidyl and Phenyl Groups on a Dendrimer Enables Efficient siRNA and DNA Delivery.

Gene therapy has received considerable attention due to its great potential in the treatment of various diseases; however, the design of efficient and biocompatible carriers for the delivery of siRNA as well as DNA still remains a major challenge. In this study, we developed an efficient carrier for gene delivery by modification of a compound containing both guanidyl and phenyl groups on the surface of a cationic dendrimer. The guanidyl group on the dendrimer facilitates nucleic acid condensation via specific guanidinium-phosphate interactions, whereas the phenyl group on the polymer is critical for efficient endosomal escape. The combination of guanidyl and phenyl shows a synergistic effect in facilitated endocytosis. The designed material is much more efficient in siRNA and DNA delivery than control materials such as dendrimers engineered with a guanidyl or phenyl group only, as well as intact dendrimers, and shows comparable efficacy to commercial transfection reagent Lipofectamine 2000. In addition, the material and its complex with nucleic acid show minimal toxicity on the transfected cells. This study provides a new strategy to develop multifunctional polymers for efficient siRNA and DNA delivery.

Adsorption of arginine, glycine and aspartic acid on Mg and Mg-based alloy surfaces: A first-principles study

Studying the adsorption behaviors of biomolecules on the surface of Mg and Mg-based alloy has a fundamental and important role for related applications in biotechnology. In the present work, we systematically investigate and compare the adsorption properties of three typical amino acids, i.e., Arg (arginine), Gly (glycine) and Asp (aspartic acid), which form RGD tripeptide, on the Mg (0001) surface with various doping (Zn, Y, and Nd), and aim to realize proper binding between biomolecules and Mg and Mg-based biomedical materials. Our results show that flat adsorption configurations of the functional groups binding to the surfaces are favored in energy for all the three selected amino acids. In specific, for the amino acids adsorped on clean Mg (0001) surface, the adsorption energy (Eads) of Arg is found to be −1.67eV for the most stable configuration, with amino and guanidyl groups binding with the surface. However, Gly (Asp) is found to binding with the surface through amino and carboxyl groups, with a −1.16eV (−1.15eV) binding energy. On the 2% Zn doped Mg (0001) alloy surface (Mg–Zn (2%)), the Eads are significantly increased to be −1.91eV, −1.32eV and −1.35eV for Arg, Gly and Asp, respectively. While the Mg–Y (1%) and Mg–Nd (1%) slightly weaken the adsorption of three amino acids. Moreover, we have performed detail discussions of the binding properties between amino acids and surfaces by projected density of states (PDOS) combined with charge transfer analyses. Our studies provide a comprehensive understanding on the interactions between amino acids and Mg and Mg-based alloy surfaces, with respect to facilitate the applications of Mg and Mg-based biomedical alloys in biosensing, drug delivery, biomolecule coating and other fields in biotechnology.

Photochemical Properties of Red-Emitting Tris(cyclometalated) Iridium(III) Complexes Having Basic and Nitro Groups and Application to pH Sensing and Photoinduced Cell Death.

Cyclometalated iridium(III) complexes, because of their photophysical properties, have the potential for use as luminescent probes for cellular imaging. We previously reported on a pH-activatable iridium complex that contains three N,N-diethylamino groups, namely, fac-Ir(deatpy)3 5, which was synthesized via a regioselective aromatic substitution reaction at the 5'-position with tolylpyridine groups of fac-Ir(tpy)3 2. It was found that 5 shows a considerable enhancement in emission intensity in the pH range from neutral to slightly acidic (pH 6.5-7.4) in aqueous solution and selectively stains lysosome in HeLa-S3 cells, due to the protonation of the diethylamino groups. In addition, 5 functions as a pH-dependent singlet oxygen ((1)O2) generator and induces necrosis-like cell death. However, observing the green emission of 5 is often hampered by autofluorescence emanating from nearby tissues. To overcome this problem, we designed and synthesized a series of new pH-activatable Ir(III) complexes that contain diethylamino, guanidyl, and iminoimidazolidinyl groups on the mpiq ligand of Ir(mpiq)3 7 and the tfpiq ligand of Ir(tfpiq)3 8, which exhibit a red emission, namely, Ir(deampiq)3 13, Ir(gmpiq)3 14, Ir(imzmpiq)3 15, and Ir(imztfpiq)3 16. The emission intensity of these Ir complexes is enhanced substantially by protonation of their basic groups, and they induce the necrosis-like cell death of HeLa-S3 cells by photoirradiation at 465 nm. A strong orange-red emission of Ir(mpiq-NO2)3 9 and Ir(tfpiq-NO2)3 10 is also reported.

L-Argininium phosphite - a new candidate for NLO materials.

In order to investigate the possibility of salt formation in the L-Arg-H3PO3-H2O system, single crystals of L-argininium phosphite, C6H15N4O2(+)·H2PO3(-), were prepared by evaporation of an aqueous solution containing equimolar quantities of L-arginine and phosphorous acid. The asymmetric unit contains one L-argininium(+) cation and one phosphite [HPO2(OH)](-) anion. The phosphite anions form chains parallel to [010] by O-H...O hydrogen bonding, with an O...O distance of 2.630 (3) Å. The protonated amine and guanidyl groups of the L-argininium(+) cations form N-H...O hydrogen bonds with the carboxylate groups and anions. The IR and Raman spectra are discussed in relation to the crystal structure. The salt displays nonlinear optical (NLO) properties. Another salt was obtained from a solution with a 1:2 molar ratio of components, but was characterized by vibrational spectra only.

Angiotensin II restricted analogs with biological activity in the erythrocytic cycle of Plasmodium falciparum.

The anti-plasmodial activity of conformationally restricted analogs of angiotensin II against Plasmodium gallinaceum has been described. To observe activity against another Plasmodium species, invasion of red blood cells by Plasmodium falciparum was analyzed. Analogs restricted with lactam or disulfide bridges were synthesized to determine their effects and constraints in the peptide-parasite interaction. The analogs were synthesized using tert-butoxycarbonyl and fluoromethoxycarbonyl solid phase methods, purified by liquid chromatography, and characterized by mass spectrometry. Results indicated that the lactam bridge restricted analogs 1 (Glu-Asp-Arg-Orn-Val-Tyr-Ile-His-Pro-Phe) and 3 (Asp-Glu-Arg-Val-Orn-Tyr-Ile-His-Pro-Phe) showed activity toward inhibition of ring formation stage of P. falciparum erythrocytic cycle, preventing invasion in about 40% of the erythrocytes. The disulfide-bridged analog 10 (Cys-Asp-Arg-Cys-Val-Tyr-Ile-His-Pro-Phe) was less effective yet significant, showing a 25% decrease in infection of new erythrocytes. In all cases, the peptides presented no pressor activity, and hydrophobic interactions between the aromatic and alkyl amino acid side chains were preserved, a factor proven important in efficacy against P. gallinaceum. In contrast, hydrophilic interactions between the Asp(1) carboxyl and Arg(2) guanidyl groups proved not to be as important as they were in the case of P. gallinaceum, while interactions between the Arg(2) guanidyl and Tyr(4) hydroxyl groups were not important in either case. The β-turn conformation was predominant in all of the active peptides, proving importance in anti-plasmodial activity. This approach provides insight for understanding the importance of each amino acid residue on the native angiotensin II structure and a new direction for the design of potential chemotherapeutic agents.