The increase in resistant bacterial strains necessitates the identification of new antimicrobial molecules. Antimicrobial peptides (AMPs) are an attractive option because of evidence that bacteria cannot easily develop resistance to AMPs. The peptaibols, a class of naturally occurring AMPs, have shown particular promise as antimicrobial drugs, but their development has been hindered by their mechanism of action not being clearly understood. To explore how peptaibols might interact with membranes, circular dichroism, vibrational circular dichroism, linear dichroism, Raman spectroscopy, Raman optical activity, neutron reflectivity and molecular dynamics simulations have been used to study a small library of peptaibol mimics, the Aib-rich peptides. All the peptides studied quickly partitioned and oriented in membranes, and we found evidence of chiral interactions between the phospholipids and membrane-embedded peptides. The protocols presented in this paper open new ground by showing how chiro-optical spectroscopies can throw light on the mechanism of action of AMPs.
- MeSH
- cirkulární dichroismus MeSH
- fosfatidylcholiny chemie MeSH
- kationické antimikrobiální peptidy chemie metabolismus MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- peptaiboly chemie metabolismus MeSH
- simulace molekulární dynamiky * MeSH
- stereoizomerie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The most demanding challenge in research on molecular aspects within the flow of biological information is posed by the complex carbohydrates (glycan part of cellular glycoconjugates). How the 'message' encoded in carbohydrate 'letters' is 'read' and 'translated' can only be unraveled by interdisciplinary efforts. SCOPE OF REVIEW: This review provides a didactic step-by-step survey of the concept of the sugar code and the way strategic combination of experimental approaches characterizes structure-function relationships, with resources for teaching. MAJOR CONCLUSIONS: The unsurpassed coding capacity of glycans is an ideal platform for generating a broad range of molecular 'messages'. Structural and functional analyses of complex carbohydrates have been made possible by advances in chemical synthesis, rendering production of oligosaccharides, glycoclusters and neoglycoconjugates possible. This availability facilitates to test the glycans as ligands for natural sugar receptors (lectins). Their interaction is a means to turn sugar-encoded information into cellular effects. Glycan/lectin structures and their spatial modes of presentation underlie the exquisite specificity of the endogenous lectins in counterreceptor selection, that is, to home in on certain cellular glycoproteins or glycolipids. GENERAL SIGNIFICANCE: Understanding how sugar-encoded 'messages' are 'read' and 'translated' by lectins provides insights into fundamental mechanisms of life, with potential for medical applications.
- MeSH
- glykoproteiny chemie MeSH
- konformace proteinů MeSH
- konformace sacharidů MeSH
- molekulární modely MeSH
- molekulární sekvence - údaje MeSH
- oligosacharidy chemie MeSH
- polysacharidy chemie MeSH
- sacharidové sekvence MeSH
- sacharidy chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
