X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair

Roethlisberger, Pascal; Marcaida, M.J.; Visini, Ricardo; Stocker, Achim; Reymond, Jean‐Louis; Leumann, Christian J.

doi:10.1039/c6cc00374e

Cited by 14 publications

(18 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(31) These are the first X-ray crystal structures of short α-helical AMPs targeting Gram-negative bacteria. This report builds on our previous examples of using LecB complexes to access structural data for molecules otherwise difficult to crystallize such as oligonucleotides, (32) glycopeptide dendrimer biofilm inhibitors, (33)(34)(35)(36)(37)(38)(39) cyclic and bicyclic AMPs. (40,41) The fucosylated peptides reported here act similarly to SB1 by folding into amphiphilic and membrane disruptive helices.…”

Section: Introductionmentioning

confidence: 90%

X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes

et al. 2019

View full text Add to dashboard Cite

Herein we report X-ray crystal structures of 11-13 residue antimicrobial peptides (AMPs) active against Pseudomonas aeruginosa as complexes of fucosylated D-enantiomeric sequences with the P. aeruginosa lectin LecB. These represent the first crystal structures of short AMPs. In twenty-four individual structures of eight different peptides we found mostly α-helices assembled as two-helix or four-helix bundles with a hydrophobic core and cationic residues pointing outside. Two of the analogs formed an extended structure engaging in multiple contacts with the lectin. Molecular dynamics (MD) simulations showed that αhelices are stabilized by bundle formation and suggested that the N-terminal acyl group present in the linker to the fucosyl group can extend the helix by one additional H-bond and increase α-helix amphiphilicity. Investigating N-terminal acylation led to AMPs with equivalent and partly stronger antibacterial effects compared to the free peptide.

show abstract

Section: Introductionmentioning

confidence: 90%

X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This fucoside appendage is used to anchor the peptide to the lectin, which crystallizes readily, a principle generally useful to access structural information on molecules otherwise difficult to crystallize. 66 , 68 , 69 Here the crystal structures showed well defined peptide macrocycles for both AMBPs, which were immobilized in the crystal lattice not only via their anchoring fucosyl group, but also through several hydrogen bonds between the peptide backbone and the lectin (Table S5, † Fig. 5a and b ).…”

Section: Resultsmentioning

confidence: 82%

Chemical space guided discovery of antimicrobial bridged bicyclic peptides against Pseudomonas aeruginosa and its biofilms

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Additionally, in literature a suppression of hole transfer processes was found for duplexes with base mismatches [18] and bulge positions, [19] suggesting that a slight perturbation of the base stack in the case of single phenanthrenyl pairs is accompanied with suppressing effects as well (see figure 3). [20] Figure 3. DNA cleavage yields for duplexes D7-D16 after 640 seconds irradiation at 420 nm.…”

Section: Nh2mentioning

confidence: 99%

Modulation of Excess Electron Transfer through LUMO Gradients in DNA Containing Phenanthrenyl Base Surrogates

Roethlisberger

Kaliginedi

Leumann

2017

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

The modulation of excess electron transfer (EET) within DNA containing a dimethylaminopyrene (C-AP) as an electron donor and 5-bromouracil ( Br dU) as a electron acceptor through phenanthrenyl pairs (phen-R) could be achieved by modifying the phenanthrenyl base surrogates with electron withdrawing and donating groups. Arranging the phenanthrenyl units to form a descending LUMO gradient increased the EET efficiency compared to the electron transfer through uniform LUMOs or an ascending LUMO gradient.The well-defined double helical structure of DNA with the linear arranged base pairs represents a suitable scaffold for charge transfer and is therefore subject to intense studies in DNA damage, [1] sensors [2] and applications in molecular electronics.[3]The reductive electron transfer also called excess electron transfer (EET) in DNA is a process that is directed through the lowest unoccupied molecular orbital (LUMO) of the DNA bases. Investigations elucidated that the charge transfer over longer distances occurs via electron hopping mostly through thymine bases (k = 10 10 s -1). [4] In earlier studies it was shown that the replacement of the natural base pairs by non-hydrogen bonding base surrogates with extended aromatic surfaces such as phenanthrene could have beneficial conducting properties and could overcome the physico-chemical limitations of the natural nucleobases.[5] Regarding the reduction of such base surrogates the choice of the electron injector is crucial for the success of the experiments. Investigations by Grigorenko et. al. revealed that pyrene ( Py dU, Ered* = -2.2 V vs NHE) [6] only enables a superexchange mechanism, whereas phenothiazine (PTZ, Ered* = -2.7 V vs SCE) [7] allowed to trigger the system into an electron hopping mechanism with a transport that spreads over longer distances.[5] A photoexcitable dimethyl amino-pyrenyl donor attached to a deoxyuracil ( AP dU, Ered* = -2.2 V vs NHE) [8] that exhibits suitable redox properties for long range charge transfer experiments was successfully used by Bätzner et. al. to inject an electron in hydroquinoline base surrogates. [9] In this study, we investigated the EET through DNA containing phenanthrenyl base surrogates with different reduction potentials and LUMO energy levels. It is believed that the electron transfer within DNA can be modulated by the installation of a potential energy gradient.[10] The predicted advantage of such a redox/LUMO gradient was envisioned to be the unidirectionality of the electron transfer and therefore a gain in efficiency. The installation of the different reduction potentials was deemed to be possible by the introduction of electron withdrawing (CN) and donating (NH2) groups at the 7-position of the phenanthrene (phen). The synthesis of the NH2 phen and phen phosphoramidites applicable for automated DNA synthesis was performed according to published procedures.[11] The introduction of a cyano group required a palladium catalyzed substitution of the intermediate 9 with copper-(I)-cyanide. Tritiylation and phosphiti...

show abstract

X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair

Cited by 14 publications

References 28 publications

X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes

X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes

Chemical space guided discovery of antimicrobial bridged bicyclic peptides against Pseudomonas aeruginosa and its biofilms

Modulation of Excess Electron Transfer through LUMO Gradients in DNA Containing Phenanthrenyl Base Surrogates

Contact Info

Product

Resources

About