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Author

Sergii Afonin

Other affiliations: University of Jena
Bio: Sergii Afonin is an academic researcher from Karlsruhe Institute of Technology. The author has contributed to research in topics: Peptide & Lipid bilayer. The author has an hindex of 32, co-authored 93 publications receiving 2794 citations. Previous affiliations of Sergii Afonin include University of Jena.


Papers
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Journal ArticleDOI
TL;DR: The membrane-disruptive antimicrobial peptide PGLa is found to change its orientation in a dimyristoyl-phosphatidylcholine bilayer when its concentration is increased to biologically active levels.

141 citations

Journal ArticleDOI
TL;DR: A system is presented in which the polypeptide backbone itself can be conformationally switched by light and the biological activity of the resulting peptidomimetics could be effectively controlled by ultraviolet/visible light within strictly defined spatial and temporal limits.
Abstract: Photobiological processes in nature are usually triggered by nonpeptidic chromophores or by modified side chains A system is presented in which the polypeptide backbone itself can be conformationally switched by light An amino acid analogue was designed and synthesized based on a reversibly photoisomerizable diarylethene scaffold This analogue was incorporated into the cyclic backbone of the antimicrobial peptide gramicidin S at several sites The biological activity of the resulting peptidomimetics could then be effectively controlled by ultraviolet/visible light within strictly defined spatial and temporal limits

134 citations

Journal ArticleDOI
TL;DR: The non‐natural amino acid 4‐fluorophenylglycine (4F‐Phg) was incorporated into several representative membrane‐associated peptides for dual purpose and its fusion activities suggest that the peptide is less structured in the fusogenic transition state than in the helical ground state.
Abstract: The non-natural amino acid 4-fluorophenylglycine (4F-Phg) was incorporated into several representative membrane-associated peptides for dual purpose. The (19)F-substituted ring is directly attached to the peptide backbone, so it not only provides a well-defined label for highly sensitive (19)F NMR studies but, in addition, the D and L enantiomers of the stiff side chain may serve as reporter groups on the transient peptide conformation during the biological function. Besides peptide synthesis, which is accompanied by racemisation of 4F-Phg, we also describe separation of the epimers by HPLC and removal of trifluoroacetic acid. As a first example, 18 different analogues of the fusogenic peptide "B18" were prepared and tested for induction of vesicle fusion; the results confirmed that hydrophobic sites tolerated 4F-Phg labelling. Similar fusion activities within each pair of epimers suggest that the peptide is less structured in the fusogenic transition state than in the helical ground state. In a second example, five doubly labelled analogues of the antimicrobial peptide gramicidin S were compared by using bacterial growth inhibition assays. This cyclic beta-sheet peptide could accommodate both L and D substituents on its hydrophobic face. As a third example, we tested six analogues of the antimicrobial peptide PGLa. The presence of d-4F-Phg reduced the biological activity of the peptide by interfering with its amphiphilic alpha-helical fold. Finally, to illustrate the numerous uses of l-4F-Phg in (19)F NMR spectroscopy, we characterised the interaction of labelled PGLa with uncharged and negatively charged membranes. Observing the signal of the free peptide in an aqueous suspension of unilamellar vesicles, we found a linear saturation behaviour that was dominated by electrostatic attraction of the cationic PGLa. Once the peptide is bound to the membrane, however, solid-state (19)F NMR spectroscopy of macroscopically oriented samples revealed that the charge density has virtually no further influence on the structure, alignment or mobility of the peptide.

116 citations

Journal ArticleDOI
TL;DR: Changes in peptide conformation and membrane alignment observed here by OCD seem to be functionally relevant, as they can be correlated with the membrane perturbing activities of the three antimicrobial and cell-penetrating sequences.

114 citations


Cited by
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Journal ArticleDOI
TL;DR: LL-37, the only cathelicidin-derived antimicrobial peptide found in humans, is shown to exhibit a broad spectrum of antimicrobial activity and has been found to have additional defensive roles such as regulating the inflammatory response and chemo-attracting cells of the adaptive immune system to wound or infection sites.

896 citations

Journal ArticleDOI
TL;DR: This poster presents a probabilistic analysis of the response of Na6(CO3)(SO4)(SO3) to Na2SO4 using a high-resolution X-ray diffraction analysis for the stationary phase.
Abstract: Department of Chemistry, Tianjin University, Tianjin 300072, China; Department of Applied Chemistry, China Agricultural University, Beijing 100193, China; UMR 6014 CNRS, Laboratoire COBRA de l’IRCOF, Université et INSA de Rouen, Rue Tesniere, F-76130 Mont Saint Aignan, France; and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China

851 citations

Journal ArticleDOI
TL;DR: Viral fusion proteins convert from a fusion-competent state to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide and the transmembrane domain into close proximity thereby facilitating the union of viral and target membranes.
Abstract: Recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. In addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. Viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. These differing features combine to yield a rich diversity of fusion proteins. Yet despite this staggering diversity, all characterized viral fusion proteins convert from a fusion-competent state (dimers or trimers, depending on the class) to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide, attached to the target membrane, and the transmembrane domain, attached to the viral membrane, into close proximity thereby facilitating the union of viral and target membranes. During these conformational conversions, the fusion proteins induce membranes to progress through stages of close apposition, hemifusion, and then the formation of small, and finally large, fusion pores. Clearly, highly divergent proteins have converged on the same overall strategy to mediate fusion, an essential step in the life cycle of every enveloped virus.

744 citations

Journal ArticleDOI
TL;DR: The fundamentals of membrane trafficking and subcellular organization are explored, as well as strategies used by pathogens to appropriate these mechanisms and the implications for drug design and delivery are explored.
Abstract: Many drug targets are localized to particular subcellular compartments, yet current drug design strategies are focused on bioavailability and tissue targeting and rarely address drug delivery to specific intracellular compartments. Insights into how the cell traffics its constituents to these different cellular locations could improve drug design. In this Review, we explore the fundamentals of membrane trafficking and subcellular organization, as well as strategies used by pathogens to appropriate these mechanisms and the implications for drug design and delivery.

637 citations