Structure Elucidation Of Pyrido[4,3-d]Pyrimidine Derivatives And Antimicrobial Peptide Phylloseptin-1Using NMR Methods

This paper is composed of two parts, one of which is1H and13C NMR assignments of three series bioactive pyrido[4,3-d]pyrimidine derivatives, the other is about the conformational study of antimicrobial peptide Phylloseptin-1(PS-1)in the Phosphate buffer and DPC micells applying CD spectrum and NMR technology.1. Pyrido-pyrimidine derivatives have been extensively studied in recent years because they are known to possess a wide range of physiological and pharmacological activities, and some of them have been reported as agricultural lead compounds possessing herbicidal and fungicidal activities. Here, the complete1H and13C NMR assignments of three series pyrido[4,3-d]pyrimidine derivatives were achieved by combination of one and two-dimensional NMR experiments.2. Given the rapid emergence of pathogens resistance against many commonly used antibiotics, development of new bactericidal and fungicidal compounds has come under spotlight all around the world. Antimicrobial peptides (AMPs) are universal host defense against invading pathogens in nearly all life forms. AMPs are quite different from traditional antibiotics both in cellular targets and mechanism of action, making them promising for alternatives to conventional antibiotics. Phylloseptins(PS-1,2,3,4,5,6) were isolated from the skin secretion of the Brazilian tree-frogs(Phyllomedusa hypochondrialis and Phyllomedusa oreades), showing anti-bacterial and anti-protozoan activities, Phylloseptin-1showed a strong antimicrobial effect against Gram-positive and Gram-negative bacteria. In this study, the conformation of Phylloseptin-1in both aqueous solution and dodecylphosphocholine (DPC-d38) micelles were examined using circular dichroism (CD) and nuclear magnetic resonance (NMR) techniques, Which showing that Phylloseptin-1lacks secondary structure in aqueous solution. However, in DPC micelles, it features with a a-helix (Ile5-Ala16) moiety and exhibits amphipathic nature, partly revealing the relationship between the structure and the antibacterial peptides activity.