Résumé
Cancer is the second leading cause of mortality worldwide preceded by cardiovascular diseases. The therapeutic approaches for drug developmentinclude the use of small molecules, antibodies, peptidesor short nucleic acid sequences. The peptide-based drugs have been developed to treat many diseases like cardiovascular diseases, cancer, metabolic disorders, immunological diseases and viral infections. More than 80 peptide drugs are already in the market. These therapeutic peptides have several important benefits over antibodies and proteins due to their small size, ease for chemical synthesis and further the ability to penetrate cell membrane. Furthermore, peptide drugs have high specificity, activity, and affinity. The plant defensins BcDef1, TPP3, NaD1, 2N2R and 2LR3 have been studied for their role in wide range of diseases. This study focussed on the conformation of plant defensins rich in disulfide bonds. The structure for BcDef1 has been predicted from the conformational ensemble. Then, we designed anticancer peptides from these defensins with computational methods. The designed anticancer peptides have been studied for their immunogenicity as well as homology with human proteome. The role of designed peptides has been suggested for interferon-gamma induction, the later has been shown to possess a very important role in cancer.
Résumé
Cancer is the second leading cause of mortality worldwide preceded by cardiovascular diseases. The therapeutic approaches for drug developmentinclude the use of small molecules, antibodies, peptidesor short nucleic acid sequences. The peptide-based drugs have been developed to treat many diseases like cardiovascular diseases, cancer, metabolic disorders, immunological diseases and viral infections. More than 80 peptide drugs are already in the market. These therapeutic peptides have several important benefits over antibodies and proteins due to their small size, ease for chemical synthesis and further the ability to penetrate cell membrane. Furthermore, peptide drugs have high specificity, activity, and affinity. The plant defensins BcDef1, TPP3, NaD1, 2N2R and 2LR3 have been studied for their role in wide range of diseases. This study focussed on the conformation of plant defensins rich in disulfide bonds. The structure for BcDef1 has been predicted from the conformational ensemble. Then, we designed anticancer peptides from these defensins with computational methods. The designed anticancer peptides have been studied for their immunogenicity as well as homology with human proteome. The role of designed peptides has been suggested for interferon-gamma induction, the later has been shown to possess a very important role in cancer.
Résumé
Cancer is the second leading cause of mortality worldwide preceded by cardiovascular diseases. The therapeutic approaches for drug developmentinclude the use of small molecules, antibodies, peptidesor short nucleic acid sequences. The peptide-based drugs have been developed to treat many diseases like cardiovascular diseases, cancer, metabolic disorders, immunological diseases and viral infections. More than 80 peptide drugs are already in the market. These therapeutic peptides have several important benefits over antibodies and proteins due to their small size, ease for chemical synthesis and further the ability to penetrate cell membrane. Furthermore, peptide drugs have high specificity, activity, and affinity. The plant defensins BcDef1, TPP3, NaD1, 2N2R and 2LR3 have been studied for their role in wide range of diseases. This study focussed on the conformation of plant defensins rich in disulfide bonds. The structure for BcDef1 has been predicted from the conformational ensemble. Then, we designed anticancer peptides from these defensins with computational methods. The designed anticancer peptides have been studied for their immunogenicity as well as homology with human proteome. The role of designed peptides has been suggested for interferon-gamma induction, the later has been shown to possess a very important role in cancer.
Résumé
RESUMEN Las plantas, al igual que todos los organismos de la naturaleza, poseen elaborados sistemas de defensa contra patógenos, que pueden ser físicos y químicos, y producirse de forma constitutiva e inducida. Dentro de las barreras químicas inducidas se encuentra el grupo de proteínas de bajo peso molecular denominadas péptidos antimicrobianos (AMPs), al cual pertenecen las defensinas, péptidos con peso molecular entre 5 a 7 kDa, punto isoeléctrico de 9, y longitud de 45 a 55 aminoácidos; que tienen la capacidad de inhibir efectivamente el crecimiento de microorganismos fitopatógenos, en su mayoría hongos, y además, generan resistencia a condiciones abióticas de estrés en plantas. Este texto pretende realizar una descripción clara y actual de las características e investigaciones recientes con relación a las defensinas de plantas y sus más destacados usos en el control de patógenos en cultivos de importancia económica. Se plantea además la necesidad de profundizar en el conocimiento de dichas proteínas para su uso en estrategias de control tales como la producción de plantas y microorganismos transgénicos.
ABSTRACT Plants, as all organisms in nature, have elaborate systems of defense against pathogens; which can be physical or chemical and produced in a constitutive and induced way. Among the induced chemical barriers, there is a group of low molecular weight proteins, known as antimicrobial peptides (AMPs). These peptides include defensins, which are peptides with a molecular weight about 5 to 7 kDa, isoelectric point of 9, and length of about 45 to 55 amino acids. Likewise, they have the ability to avoid the growth of phytopathogenic microorganisms, mainly funguses. Moreover, these peptides create resistance to abiotic conditions of stress in plants. This manuscript seeks to make a clear and current description about the recent characteristics and researches related to plant defensins and their most significant uses in pathogens management in crops of economical relevance. It also intends to go deep into the study of such proteins in order to use them as a control strategy, such as production of transgenic plants and microorganisms.
Résumé
Se aislaron y caracterizaron parcialmente proteínas antifúngicas de los espacios intercelulares de hojas de tomate Lycopersicon esculentum cerasiforme, variedad que ha mostrado resistencia en campo a Phytophthora Infestans; se observó que después de inoculación con el patógeno dichas proteínas se acumularon sistémicamente en la planta. Las proteínas identificadas mostraron características de Defensinas de plantas, una nueva familia de proteínas con bajo peso molecular, carga positiva a pH fisiológico y actividad antifúngica evaluada in vitro contra P. infestans. Los análisis electroforéticos en geles de poliacrilamida con SDS-Tricina en condiciones reductoras y no reductoras, sugirieron que están asociadas en trímeros y tetrámeros y poseen pesos moleculares de 5,2 kDa.
Antifungal Proteins from intercellular space of Tomato leaves Lycopersicon esculentum cerasiforme were isolated and partially characterized; this variety had shown resistance against Phytophthora infestans, after inoculating plants with the pathogen it was observed that these proteins were accumulated systemically. The isolated proteins be haved as plant defensins, a novel protein family, with low molecular weight, cationics at physiological pH and Antifungal Activity in vitro evaluated against P. infestans. Electrophoretic analyses in SDS Tricine-PAGE, under reducing and non-reducing conditions suggested that, they were associated as trimers and tetramers; and have molecular weights of 5,2 kDa.