RESUMO
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.
RESUMO
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.
RESUMO
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.
RESUMO
The non-proteinogenic amino acids — phenylglycine (PG) and hydroxyphenylglycine (HPG) are crucial components of certain peptidic natural products and are important for the preparation of various medicines. In this, study, the conformation of model dipeptides Ac-X-NHMe of PG, p-HPG and 3, 5-di-hydroxyphenylglycine (3, 5-DHPG) was studied both in R and S form by quantum mechanical (QM) and molecular dynamics approaches. On the energy scale, the conformational states of these molecules in both the R and S were found to be degenerate by QM studies, stabilized by non-covalent interactions like carbonyl--carbonyl interactions, carbonyl-lp··π (aromatic ring) interactions etc. These interactions disappeared/weakened due to interaction of water molecules with carbonyl groups of backbone in simulation and water was found to interact with the aromatic ring through Ow-H··π or Owlp··π interactions. The degeneracy of conformational states was lifted in favor of R-form of PG and DHPG and water molecules interactions with aromatic ring led to non-planarity of the aromatic ring. In simulation studies, irrespective of the starting geometry, the , values for the R form correspond to inverse b/inverse collagen region and for the S-form, the , values correspond to b/collagen region i.e., adopt single conformation. The obtained results were in conformity with the CD spectroscopic data on D-PG and D-p-HPG. The conformational behavior of the unusual amino acids might be of great help in designing of bioactive peptides/peptide based drugs to be realized in single conformation – an essential requirement.