Background: The resurgence of Mycobacterium tuberculosis (Mtb) strains that resist anti-tuberculosis (anti-TB) drugs used currently stresses the search for more effective low-toxicity drugs against new targets. Due to their role in ion homeostasis and virulence, Mtb plasma membrane P-type ATPases are interesting anti-TB targets, in particular, the Ca2+ transporting P2-type ATPase CtpF which is involved in oxidative stress response and persistence. Methods: In this study, the effect on the transcription level of the ctpF gene and other Mtb P2-type ATPases of two anti-Mtb hits was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Both anti-Mtb hits ZINC14541509 and ZINC63908257 had been previously identified using pharmacophore-based virtual screening and MM-GBSA binding free energy. In addition, the bacterial activity of both compounds on Mycobacterium bovis was evaluated to see whether or not there is an effect on other mycobacteria of the Mtb complex. Results: qRT-PCR experiments showed that the ctpF transcription level was significantly higher in the presence of both compounds, especially ZINC14541509, strongly suggesting that CtpF may be a specific target of the selected compound. Conclusions: ZINC14541509 should be considered as an alternative for the structural-based design of novel anti-TB drugs.
Mycobacterium tuberculosis , P-type ATPases , Humans , Mycobacterium tuberculosis/genetics , Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/pharmacology , Membrane Transport Proteins/genetics , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry
Introducción: La pandemia de la COVID-19 ha generado un incremento de la información sobre esta enfermedad, por lo que es fundamental garantizar la credibilidad y confiabilidad de las páginas web que brindan esta información. Objetivo: Evaluar la confiabilidad de la información sanitaria en español sobre la COVID-19 en el motor de búsqueda Google considerando los criterios de la herramienta HONcode. Material y métodos: Estudio observacional de corte transversal. Las páginas web de Google se analizaron en diciembre del 2020 desde Lima-Perú, utilizando 4 términos de búsqueda. Se evaluó la confiabilidad de la información sanitaria de las páginas web mediante la herramienta HONcode (versión 3.1.3). Se clasificaron según la fuente de información y su procedencia. El análisis estadístico se realizó para un nivel de significancia de p<0,05. Resultados: Se evaluaron 200 páginas web en español, el 16,5% poseían certificado HONcode, la mayoría fue de la OMS (33,3%), la principal fuente de información fue "académica-profesional" (30,0%). Además, el 33,0% de las páginas web eran peruanas, siendo mayormente de tipo gubernamental (42,4%), pero ninguna tenía certificado HONcode. Conclusiones: Solo una de cada seis páginas web proporcionaba información sanitaria confiable sobre la COVID-19. Además, se distingue la presencia de las páginas web de la OMS en proveer información sanitaria sobre la COVID-19 en Google. Si bien este estudio destaca las páginas web de organismos internacionales, se requiere fortalecer la comunicación desde las páginas web gubernamentales peruanas.
Introduction: The COVID-19 pandemic has generated an increase in information about this disease, so it is essential to ensure the credibility and reliability of the web pages that provide this information. Objective: To evaluate the reliability of health information in Spanish on COVID-19 in the Google search engine considering the criteria of the HONcode tool. Material and methods: Observational cross-sectional study. Google web pages were analyzed in December 2020 from Lima-Peru, using 4 search terms. The reliability of the health information on the web pages was assessed using the HONcode tool (version 3.1.3). They were classified according to the source of information and its provenance. Statistical analysis was performed for a significance level of p<0.05. Results: 200 web pages in Spanish were evaluated, 16.5% were HONcode certified, most of them were from the WHO (33.3%), the main source of information was "academic-professional" (30.0%). In addition, 33.0% of the web pages were Peruvian, being mostly governmental (42.4%), but none had HONcode certificate. Conclusions: Only one out of six web pages provided reliable health information on COVID-19. In addition, the presence of WHO web pages in providing health information about COVID-19 on Google stands out. Although this study highlights the web pages of international organizations, there is a need to strengthen communication from Peruvian governmental web pages.
Objectives: To evaluate the reliability of health information in Spanish on COVID-19 in Google, considering the criteria of the HONcode tool. Materials and methods: Observational cross-sectional study. Google web pages were obtained in December 2020 using 4 search terms. The reliability of the health information of the web pages was evaluated using the HONcode tool (version 3.1.3). Also, they were classified according to the source of information and procedence; the statistical analysis was performed considering as significant value for p<0,05. Results: 200 web pages in Spanish were evaluated, 16,5% had the HONcode certificate; belonging, in majority, to the WHO website (33,3%). The main source of information was "academic-professional" (30,0%). Regarding the origin, 33,0% of the web pages were Peruvian, mostly from governmental source (42,4%), but none had the HONcode certificate. HONcode certificate for the web pages were found for all search terms; however, the association was not statistically significant (p=0,876). The first page of results in Google was more likely (32,5%) to contain HONcode certified web pages (p=0,012). Conclusion: At least one of six websites provided reliable health information about COVID-19. Moreover, the presence of WHO websites in providing COVID-19 health information on Google is distinguished. Whereas this study highlights the websites of international organizations, it is necessary to strengthen communication from Peruvian government websites.
Objetivo: Evaluar la confiabilidad de la información sanitaria en español sobre la COVID-19 en el motor de búsqueda Google considerando los criterios de la herramienta HONcode. Materiales y métodos: Estudio observacional de corte transversal. Las páginas web de Google se obtuvieron en diciembre del 2020 utilizando 4 términos de búsqueda. Se evaluó la confiabilidad de la información sanitaria de las páginas web mediante la herramienta HONcode (versión 3.1.3). También, se clasificaron según la fuente de información y su procedencia. El análisis estadístico se realizó para un nivel de significancia de p<0,05. Resultados: Se evaluaron 200 páginas web en español, el 16,5% poseían el certificado HONcode siendo en su mayoría del sitio web de la OMS (33,3%). La principal fuente de información fue "académica-profesional" (30,0%). En cuanto a la procedencia, el 33,0% de las páginas web eran peruanas, siendo en su mayoría de tipo gubernamental (42,4%), pero ninguna con certificado HONcode. Se hallaron páginas web con certificado HONcode para todos los términos de búsqueda; sin embargo, la asociación no fue estadísticamente significativa (p=0,876). La primera página de resultados en Google tenía más probabilidad (32,5%) de contener páginas web con certificado HONcode (p=0,012). Conclusión: Solo una de cada seis páginas web proporcionaba información sanitaria confiable sobre la COVID-19. Además, se distingue la presencia de las páginas web de la OMS en proveer información sanitaria sobre la COVID-19 en Google. Si bien este estudio destaca las páginas web de organismos internacionales, se requiere fortalecer la comunicación desde las páginas web gubernamentales peruanas.
La biopelícula como un mecanismo de virulencia en Staphylococcus involucrada en infecciones intrahospitalarias es regulada por un represor negativo icaR, responsable de la transcripción completa del operón icaADBC. La búsqueda de dominios funcionales por modulación computacional de icaR permitió hallar las secuencias peptídicas con actividad biológica análoga a la proteína icaR. Mediante biología computacional se diseñaron péptidos empleando el programa de predicción AntiBP (http://www.imtech.res.in/raghava/antibp/); la síntesis química se hizo por Nα-Fmoc y se caracterizaron y purificaron tres moléculas por RP-HPLC y MALDI-TOF. Se evaluó su seguridad biológica mediante ensayo de actividad citotóxica realizada sobre macrófagos murinos de la línea J774 y la actividad hemolítica se determinó mediante el uso de glóbulos rojos. Los tres péptidos caracterizados IR1, IR2 e IR3, presentaron estructura secundaria predominantemente alfa helicoidal, alto grado de pureza y alto score antimicrobiano; además, mostraron baja toxicidad, evidenciada por la actividad citotóxica y hemolítica en las concentraciones ensayadas y en comparación con los controles usados, que permitiría su potencial uso como moléculas candidatas o principios activos con actividad análoga al represor nativo icaR, frente a la biopelícula de los Staphylococcus sp.
Staphylococcus sp. biofilm, formed as a mechanism of virulence that is involved in hospital acquired infections, is regulated by a negative repressor icaR, which is responsible for the full transcription of the operon icaADBC. This study, through functional commands by computational modulation of icaR, allowed to find peptide sequences with similar biological activity to the icaR protein. Peptides were designed by means of computational biology using the prediction program AntiBP (http://www.imtech.res.in/raghava/antibp/). The chemical synthesis of peptides was performed by Nα-Fmoc. The purification and characterization of three molecules were carried out using RP-HPLC and MALDI-TOF. Biological safety of peptides was evaluated by tests of cytotoxic activity on murine macrophage cells line J774, and their hemolytic activity was determined by using red cells. The three characterized peptides IR1, IR2 and IR3 presented a predominantly secondary alpha helical structure with a high degree of purity and high antimicrobial scores. In addition, the peptides exhibited low toxicity, proved by their low cytotoxic and hemolytic activity in the tested concentrations and in comparison to the standards used. These results allow the potential use of these peptides as candidate molecules or active principles with similar activity to the native repressor icaR against the Staphylococcus biofilm.
O biofilme formado como um mecanismo de virulência em Staphylococcus sp., que está envolvido com infecções intra-hospitalares, é regulado por um repressor negativo icaR, o qual é responsável pela plena transcrição do operão icaADBC. Por tanto, o presente estudo, avaliando a segurança biológica de moléculas, concebeu peptídeos antibiofilme semelhantes ao repressor icaR. Por meio da biologia computacional foram concebidos peptídeos usando o programa de predição AntiBP (http://www.imtech.res.in/raghava/antibp/) para identificar as sequências com uma atividade biologicamente similar à da proteína icaR. A Síntese química dos peptídeos se fez pelo Nα-Fmoc e foram caracterizadas e purificadas três moléculas por RP-HPLC e MALDI-TOF. O ensaio de atividade citotóxica foi realizado nos macrófagos murinos da linha J774 e a atividade hemolítica foi determinada por meio do uso de glóbulos vermelhos. Foram caraterizados três peptídeos IR1, IR2 e IR3, além de mostrarem uma estrutura secundaria predominantemente alfa helicoidal, com alto grau de pureza, alto score antimicrobiano e baixa toxicidade, estes podem ser postulados como moléculas candidatas ou princípios ativos com uma atividade similar ao repressor nativo icaR frente ao biofilme dos Staphylococcus sp.
BACKGROUND: The TlyA protein has a controversial function as a virulence factor in Mycobacterium tuberculosis (M. tuberculosis). At present, its dual activity as hemolysin and RNA methyltransferase in M. tuberculosis has been indirectly proposed based on in vitro results. There is no evidence however for TlyA relevance in the survival of tubercle bacilli inside host cells or whether both activities are functionally linked. A thorough analysis of structure prediction for this mycobacterial protein in this study shows the need for reevaluating TlyA's function in virulence. RESULTS: Bioinformatics analysis of TlyA identified a ribosomal protein binding domain (S4 domain), located between residues 5 and 68 as well as an FtsJ-like methyltranferase domain encompassing residues 62 and 247, all of which have been previously described in translation machinery-associated proteins. Subcellular localization prediction showed that TlyA lacks a signal peptide and its hydrophobicity profile showed no evidence of transmembrane helices. These findings suggested that it may not be attached to the membrane, which is consistent with a cytoplasmic localization. Three-dimensional modeling of TlyA showed a consensus structure, having a common core formed by a six-stranded ß-sheet between two α-helix layers, which is consistent with an RNA methyltransferase structure. Phylogenetic analyses showed high conservation of the tlyA gene among Mycobacterium species. Additionally, the nucleotide substitution rates suggested purifying selection during tlyA gene evolution and the absence of a common ancestor between TlyA proteins and bacterial pore-forming proteins. CONCLUSION: Altogether, our manual in silico curation suggested that TlyA is involved in ribosomal biogenesis and that there is a functional annotation error regarding this protein family in several microbial and plant genomes, including the M. tuberculosis genome.
Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Hemolysin Proteins/chemistry , Hemolysin Proteins/metabolism , Models, Molecular , Molecular Sequence Annotation , Mycobacterium tuberculosis , Amino Acid Sequence , Animals , Bacterial Proteins/genetics , Computational Biology , DNA Restriction Enzymes/genetics , Evolution, Molecular , Hemolysin Proteins/genetics , Humans , Intracellular Space/metabolism , Mice , Molecular Sequence Data , Mycobacterium tuberculosis/cytology , Mycobacterium tuberculosis/pathogenicity , Operon/genetics , Protein Conformation , Protein Transport , Reproducibility of Results , Research Design , Transcription, Genetic , Virulence Factors/chemistry , Virulence Factors/genetics , Virulence Factors/metabolism
The Plasmodium falciparum merozoite surface protein 1 has been studied due to its potential to becomea vaccine; likewise, the peptide 1585 which is located in the 42-kDa amino-terminal fragment inducesprotective immunity in primates. Despite the importance of antigen adsorption in the formulation andproduction of vaccines containing aluminium adjuvant, the protein fragment adsorption on aluminium hydroxide has not been thoroughly studied. Electrostatic attraction, hydrophobic interaction and ligand exchange have been identified as the major mechanisms involved in antigen retention on the adsorbent surface. Peptide 1585 was synthesized, and its solubility, adsorption on aluminium hydroxide, as well as its molecule release have been studied here. Results allowed us to raise a model for the adsorption and release of this peptide, which are important parameters to establish optimal conditions for peptide adsorbent interaction and, therefore, their response as a vaccine. Results also established the reversibility of such process due to the phosphate ion effect. Thus, this work provides a starting point for research works, leading to further development of vaccine formulations containing highly purified synthetic antigens adsorbed on aluminium adjuvant.
Absorption , Plasmodium
Plasmodium vivax malaria is one of the most prevalent parasitic diseases in Asia and Latin-America. The difficulty of maintaining this parasite culture in vitro has hampered identifying and characterising proteins implied in merozoite invasion of red blood cells. We have been able to identify an open reading frame in P. vivax encoding the Plasmodium falciparum merozoite surface protein 10 homologous protein using the partial sequences from this parasite's genome reported during 2004. This new protein contains 479 amino-acids, two epidermal growth factor-like domains, hydrophobic regions at the N- and C-termini, being compatible with a signal peptide and a glycosylphosphatidylinositol anchor site, respectively. The protein is expressed during the parasite's asexual stage and is recognised by polyclonal sera in parasite lysate using Western blot. P. vivax-infected patients' sera highly recognised recombinant protein by ELISA.
Plasmodium falciparum/chemistry , Plasmodium vivax/chemistry , Protozoan Proteins/chemistry , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA Primers , Molecular Sequence Data , Protein Conformation , Rabbits , Sequence Homology, Amino Acid
Plasmodium vivax, one of the four parasite species causing malaria in humans, is the most widespread throughout the world, leading to nearly 80 million cases per year, mainly in Latin-America and Asia. An open reading frame encoding the Plasmodium falciparum merozoite surface protein 8 P. vivax homologue has been identified in the present study by screening the current data obtained from this parasite's partially sequenced genome. This new protein contains 487 amino-acids, two epidermal growth factor like domains, hydrophobic regions at the N- and C-termini compatible with a signal peptide, and a glycosylphosphatidylinositol anchor site, respectively. This gene's transcription and its encoded protein expression have been assessed, as well as its recognition by P. vivax-infected patients' sera. Based on this recognition, and a previous study showing that mice immunised with the Plasmodium yoelii homologous protein were protected, we consider the PvMSP8 a good candidate to be included in a multi-stage multi-antigen P. vivax vaccine.
Antigens, Protozoan/genetics , Antigens, Protozoan/immunology , Plasmodium vivax/immunology , Protozoan Proteins/genetics , Protozoan Proteins/immunology , Amino Acid Motifs , Amino Acid Sequence , Animals , Antibodies, Protozoan/blood , Antigens, Protozoan/metabolism , Cloning, Molecular , Epidermal Growth Factor/chemistry , Gene Expression , Humans , Molecular Sequence Data , Plasmodium vivax/genetics , Plasmodium vivax/growth & development , Protozoan Proteins/metabolism
This study reports the molecular characterization and tissue expression of the non-human Aotus nancymaae primate CD1b isoform in the search for an experimental animal model to be used in evaluating the role of non-peptide antigen-presentation molecules in the immune response to infectious agents. CD1b expression on the surface of A. nancymaae peripheral blood monocyte-derived dendritic cells, shown by flow cytometry, was made possible by using human CD1b isoform antibodies. Studying the expression of CD1b-encoded transcripts revealed this molecule's broad distribution in several tissues. The A. nancymaae CD1b transcript-encoded amino-acid sequence showed 95.5% identity with the human sequence. Such high sequence homology was reflected in the identical structural conservation of how pockets A', C' and F' and tunnel T' conforming the antigen's binding site are organized, the similar arrangement of those amino-acids interacting with the T-cell receptor (TCR) during antigen presentation, and the conservation of YQNI-motif sequence in the cytoplasmatic tail (responsible for the molecule's intracellular trafficking in humans). Comparing the structure of human CD1a and CD1b and mouse CD1d proteins with CD1b structure in A. nancymaae obtained by minimization revealed that changes in the latter molecule's alpha1 and alpha2 domains imposed a narrowing of the antigen-binding groove in A. nancymaae CD1b. The high structural similarity between A. nancymaae CD1b and that from humans presented in this study leads to A. nancymaae being proposed as a suitable experimental animal model for analyzing CD1b in vivo, mainly in bacterial and parasite infections such as tuberculosis and malaria, respectively.
Antigens, CD1/metabolism , Dendritic Cells/metabolism , Monocytes/metabolism , Amino Acid Sequence , Animals , Antigen Presentation , Antigens, CD1/chemistry , Antigens, CD1/genetics , Aotidae , Binding Sites , Cloning, Molecular , Conserved Sequence , Dendritic Cells/cytology , Disease Models, Animal , Flow Cytometry , Humans , Mice , Molecular Sequence Data , Monocytes/cytology , Protein Conformation , Protein Folding , Receptors, Antigen, T-Cell/chemistry , Receptors, Antigen, T-Cell/metabolism , Sequence Homology, Amino Acid , Tissue Distribution
The Plasmodium falciparum acidic-basic repeat antigen represents a potential malarial vaccine candidate. One of this protein's high activity binding peptides, named 2150 ((161)KMNMLKENVDYIQKNQNLFK(180)), is conserved, non-immunogenic, and non-protection-inducing. Analogue peptides whose critical binding residues (in bold) were replaced by amino-acids having similar mass but different charge were synthesized and tested to try to modify such immunological properties. These analogues' HLA-DRbeta1* molecule binding ability were also studied in an attempt to explain their biological mechanisms and correlate binding capacity and immunological function with their three-dimensional structure determined by (1)H NMR. A 3(10) distorted helical structure was identified in protective and immunogenic peptide 24922 whilst alpha-helical structure was found for non-immunogenic, non-protective peptides having differences in alpha-helical position. The changes performed on immunogenic, protection-inducing peptide 24922 allowed it to bind specifically to the HLA-DRbeta1*0301 molecule, suggesting that these changes may lead to better interaction with the MHC Class II-peptide-TCR complex rendering it immunogenic and protective, thus suggesting a new way of developing multi-component, sub-unit-based anti-malarial vaccines.
Antigens, Protozoan/chemistry , Antigens, Protozoan/pharmacology , HLA-DR Antigens/chemistry , HLA-DR Antigens/pharmacology , Models, Molecular , Plasmodium falciparum/drug effects , Protozoan Proteins/chemistry , Protozoan Proteins/pharmacology , Amino Acid Sequence , Amino Acid Substitution , Animals , Antigens, Protozoan/immunology , Binding Sites , Computer Simulation , Drug Design , HLA-DR Antigens/immunology , Haplorhini , Malaria Vaccines/administration & dosage , Malaria Vaccines/chemistry , Malaria Vaccines/immunology , Molecular Sequence Data , Peptides/chemistry , Plasmodium falciparum/immunology , Protein Binding , Protein Conformation , Protein Structure, Secondary , Protozoan Proteins/immunology , Structure-Activity Relationship
Human papillomavirus type 16 (HPV-16) represents the major cervical carcinoma associated virus among women, especially in Colombia. It has thus become important to develop reliable inexpensive tests for detecting the presence of this virus. It has been shown that HPV16-E7 oncoprotein structural features have three alpha-helical structures and a loop-like structure. The hydrazone link approach was used to mimic helix secondary substructures. Sera from women with invasive cervical carcinoma were tested against conformationally restricted peptides and their respective linear peptides to identify conformational epitopes. One peptide that was conformationally restricted to an alpha-helix showed very strong positive reaction with sera from women having invasive cervical carcinoma; there was no reaction with sera from patients with other carcinomas, children, or healthy women. NMR studies confirmed this peptide's alpha-helical structure. The observation that constrained protein substructure peptidomimetics can identify new conformationally sensitive antibodies in cervical carcinoma patients' sera is very important, since these antibodies are almost all generated by native proteins, providing a new selection of antibodies for diagnostic and vaccine studies.
Oncogene Proteins, Viral/chemistry , Peptides/chemistry , Uterine Cervical Neoplasms/diagnosis , Child , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hydrazones/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Mimicry , Papillomavirus E7 Proteins , Protein Structure, Secondary , Serologic Tests/methods , Serum , Uterine Cervical Neoplasms/blood
The merozoite surface protein-1 represents a prime candidate for development of a malaria vaccine. Merozoite surface protein-1 has been shown to demonstrate high-activity peptide binding to human red blood cells. One of the high-activity binding peptides, named 5501, located in the N-terminus (amino acid sequence MLNISQHQCVKKQCPQNS) of the 19-kDa molecular mass fragment of merozoite surface protein-1, is conserved, nonimmunogenic and nonprotective. Its critical binding residues were identified and replaced with amino acids of similar mass but different charge, in order to modify their immunogenic and protective characteristics. Three analogues with positive or negative immunological results were studied by nuclear magnetic resonance to correlate their three-dimensional structure with their biological functions. The studied peptides presented alpha-helical fragments, but in different peptide regions and extensions, except for randomly structured 5501. We show that altering a few amino acids induced immunogenicity and protectivity against experimental malaria and changed the peptide three-dimensional structure, suggesting a better fit with immune-system molecules.
Malaria/prevention & control , Merozoite Surface Protein 1/chemistry , Peptides/chemistry , Peptides/pharmacology , Amino Acid Sequence , Animals , Aotidae , Binding Sites , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Sequence Data , Peptide Fragments/chemistry , Peptides/immunology , Peptides/metabolism , Protein Conformation , Structure-Activity Relationship
A conserved high activity erythrocyte binding peptide (HAEBP) derived from the 175-erythrocyte binding antigen (EBA-175), coded 1758, was synthesized and analyzed for antigenic and protective activities in Aotus monkeys, together with several of its analogues. Conformational analysis by 1H Nuclear Magnetic Resonance in TFE-solution was done for some of them, as well as the 1758 parent peptide. We show that the conserved 1758 HAEBP (being neither immunogenic nor protective) has an alpha helical structure, whilst its analogues contain beta-turn structures. The 13790 peptide (highly immunogenic and protective for some monkeys) shows a type I beta-turn structure distorted in psi(i + 1) psi(i + 2) angles, whilst immunogenic and non-protective (as well as the non-immunogenic and non-protective peptides) have type III' beta-turns. An understanding of native peptide's correlation with altered peptide three-dimensional structure and resulting immunogenicity and protective activity may lead to a more rational design of multi-antigenic, multi-stage P. falciparum subunit based malaria vaccines.
Erythrocytes/metabolism , Malaria, Falciparum/prevention & control , Peptide Fragments/metabolism , Plasmodium falciparum/metabolism , Protozoan Proteins/metabolism , Amino Acid Sequence , Animals , Blotting, Western , Erythrocytes/parasitology , Fluorescent Antibody Technique, Indirect , Haplorhini , Molecular Sequence Data , Nuclear Magnetic Resonance, Biomolecular , Peptide Fragments/chemistry , Plasmodium falciparum/physiology , Protein Conformation , Protons , Protozoan Proteins/chemistry , Sequence Homology, Amino Acid
One Plasmodium falciparum malaria antigen is an integral membrane protein called apical membrane antigen-1. High activity binding peptides to human red blood cells have been identified in this protein. 4337 is a conserved, non-immunogenic peptide with high activity red blood cell binding and its critical residues have already been identified. Peptide analogues (with amino acids having the same mass but different charge) were generated to change their immunogenic and protective characteristics. Three analogues having positive or negative immunological results were studied by nuclear magnetic resonance. The studied peptides all had an alpha-helix fragment, but in different peptide regions and extensions, except for randomly structured 4337. We show that altering a few amino acids induced immunogenicity and protectivity against experimental malaria and changed their three-dimensional structure, suggesting a better fit with immune system molecules and that modified peptides having better immunological properties can be included in the design of new malaria multi-component subunit-based vaccine.
Antigens, Protozoan , Malaria, Falciparum/immunology , Membrane Proteins/chemistry , Membrane Proteins/immunology , Peptides/chemistry , Peptides/immunology , Protozoan Proteins/chemistry , Protozoan Proteins/immunology , Amino Acid Sequence , Animals , Haplorhini , Magnetic Resonance Spectroscopy , Malaria Vaccines/chemistry , Malaria Vaccines/pharmacology , Malaria, Falciparum/prevention & control , Membrane Proteins/pharmacology , Molecular Sequence Data , Peptides/pharmacology , Protein Conformation , Protozoan Proteins/pharmacology , Structure-Activity Relationship
