Antimicrobial peptides (AMPs) are promising next generation antibiotics that hold great potential for combating bacterial resistance. AMPs can be both bacteriostatic and bactericidal, induce rapid killing and display a lower propensity to develop resistance than do conventional antibiotics. Despite significant progress in the past 30 years, no peptide antibiotic has reached the clinic yet. Poor understanding of the action mechanisms and lack of rational design principles have been the two major obstacles that have slowed progress. Technological developments are now enabling multidisciplinary approaches including molecular dynamics simulations combined with biophysics and microbiology toward providing valuable insights into the interactions of AMPs with membranes at atomic level. This has led to increasingly robust models of the mechanisms of action of AMPs and has begun to contribute meaningfully toward the discovery of new AMPs. This review discusses the detailed action mechanisms that have been put forward, with detailed atomistic insights into how the AMPs interact with bacterial membranes. The review further discusses how this knowledge is exploited toward developing design principles for novel AMPs. Finally, the current status, associated challenges, and future directions for the development of AMP therapeutics are discussed.

Amelogenins make up a class of proteins associated with the formation of mineralized enamel in vertebrates, possess highly conserved N-and C-terminal sequence regions, and represent an interesting model protein system for understanding biomineralization and protein assembly. Using bioinformatics, we report here the identification of molecular traits that classify 12 amelogenin proteins as members of the intrinsically disordered or unstructured protein family (IDPs), a group of proteins that normally exist as unfolded species but are capable of transformation to a folded state as part of their overall function. Using biophysical techniques (CD and NMR), we follow up on our bioinformatics studies and confirm that one of the amelogenins, recombinant porcine rP172, exists in an extended, unfolded state in the monomeric form. This protein exhibits evidence of conformational exchange between two states, and this exchange may be mediated by Pro residues in the sequence. Although the protein is globally unfolded, we detect the presence of local residual secondary structure [α-helix, extended β-strand, turn/loop, and polyproline type II (PPII)] that may serve several functional roles within the enamel matrix. The extended, labile conformation of rP172 amelogenin is compatible with the known functions of amelogenin in enamel biomineralization, i.e., self-assembly, associations with other enamel matrix proteins and with calcium phosphate biominerals, and interaction with cell receptors. It is likely that the labile structure of this protein facilitates interactions of amelogenin with other macromolecules or with minerals for achievement of internal protein stabilization.The formation of inorganic compounds by organisms (biomineralization) is a substantial scientific puzzle. The ability of cells to employ proteins to control nucleation, crystal morphology, polymorphism, and the material properties of living tissues requires precise molecular control and efficient mechanisms (1). One such protein, amelogenin, is found in mammalian tooth enamel, one of the most highly mineralized materials of vertebrates (1-3). Amelogenin is essential for normal enamel development and is capable of protein selfassociation, forming supramolecular assemblies under defined conditions in the laboratory (4-6). These supramolecular assemblies (nanospheres) are believed to exert control over the † This work was supported by funding from the Department of Energy (DE-FG02-03ER46099) and the National Institute of Dental and Craniofacial Research (DE-013414 morphology, organization, and directionality of hydroxyapatite crystal growth (7,8). Primary sequence analysis of 26 mammalian lineages indicates that the N-terminus (Tyr-rich) and Cterminus (charged) of amelogenin are highly conserved, whereas variations occur in the central regions (9). Amelogenin sequence mutations lead to defective enamel crystal formation and organization (10,11), and deletion of the conserved terminal domains leads to the formation of ill-defined enamel crystals, high...

Nanotechnology refers to the fabrication, characterization, and application of substances in nanometer scale dimensions for various ends. The influence of nanotechnology on the healthcare industry is substantial, particularly in the areas of disease diagnosis and treatment. Recent investigations in nanotechnology for drug delivery and tissue engineering have delivered high-impact contributions in translational research, with associated pharmaceutical products and applications. Over the past decade, the synthesis of nanofibers or nanoparticles via electrostatic spinning or spraying, respectively, has emerged as an important nanostructuring methodology. This is due to both the versatility of the electrospinning/electrospraying process and the ensuing control of nanofiber/nanoparticle surface parameters. Electrosprayed nanoparticles and electrospun nanofibers are both employed as natural or synthetic carriers for the delivery of entrapped drugs, growth factors, health supplements, vitamins, and so on. The role of nanofiber/nanoparticle carriers is substantiated by the programmed, tailored, or targeted release of their contents in the guise of tissue engineering scaffolds or medical devices for drug delivery. This review focuses on the nanoformulation of natural materials via the electrospraying or electrospinning of nanoparticles or nanofibers for tissue engineering or drug delivery/pharmaceutical purposes. Here, we classify the natural materials with respect to their animal/plant origin and macrocyclic, small molecule or herbal active constituents, and further categorize the materials according to their proteinaceous or saccharide nature.

Various methods to synthesize diverse nanoparticles with their different applications.