KemiForskerne er opdelt efter fagomrade. I kemi skelnes der mellem teoretisk kemi, molekylær og supramolekylær kemi, materialekemi, organisk syntese, nukleinsyrekemi samt medicinalkemi.

Teoretisk kemi

Hans Jørgen Aagaard ............................................................................................ 3

Jacob Kongsted ..................................................................................................... 5

Molekylær og supramolekylær kemi

Christine McKenzie .............................................................................................. 6

Materialekemi

Changzhu Wu ....................................................................................................... 7

Dorthe Ravnsbæk ................................................................................................. 8

Ulla Gro Nielsen ................................................................................................... 9

Organisk syntese

Jan O. Jeppesen ................................................................................................... 10

Steffen Bahring ................................................................................................... 11

Himanshu Khandelia ............................................................................................ 4

Nukleinsyrekemi

Jesper Wengel ................................................................................................... 12

Michael Petersen ............................................................................................... 13

Poul Nielsen ...................................................................................................... 14

Stefan Vogel ...................................................................................................... 15

Medicinalkemi

Jasmin Mecinović .............................................................................................. 16

☺

☺

☺

We develop new, efficient and flexible metods in Dirac. In 2015 we were chosen by Oak Ridge Naitional Laboratory as one of 13 programs they would hellp optimizie for their supercompter Summit, which was opened for use Jan. 2019 and it is now number 1 in the world.

• • • • • 

Professor Christine J. McKenzieMetal-organic, Bioinorganic

and Green Chemistry

Catalysis

email: mckenzie@sdu.dkweb: http://mckee.sdu.dk/cjmck/home.html

Radiotheranostics

Solvent-free reactionsJust like the gas processing enzymes, small molecules arechemisorbed by our new metal-organic materials.Reactions include reversible gas binding and toxic gascapture and conversion.

(a) Active site structure of a material that grabs O2 from air (b) Section of X-ray structure showing the chemisorbed O2(c) Visible color changes on sorption and desorption.

Copper ”metal-organic framework” that can reversibly bind NH3.

QR-code forYoutube Video:

Collaboration with the Water Research Center, University of New South Wales, Sydney, AUS.

Single crystal X-ray crystallographyCo-supervisor Adjunkt prof. Vickie McKee Collaboration with Assoc. Prof. Helge Thisgaard at OUH-nuclear medicine

O OH COOH

OH

O

OH

N

N

N

N

N

FeIVO

N

N

NNN

FeIVO

NN

NN

NFeIV

O

Spiders are blue-blooded - they reversiblybind O2 at the dicopper site of hemocyanin.

Industrial processes are far from achieving enzyme-like selectivity, atom- and energy-efficiency. We synthesizenew metal-organic compounds with biomimetic active sites with one aim being discovery of new technologies foralleviating the emission of Greenhouse (CO2, CH4) and toxic gases (NOx) from anthropogenic activities.

Auger Electron Emitters (AEEs) hold great promise in targetedradionuclide therapy for cancer. Short decay paths means celldestruction can occur without extensive damage to surroundingtissues. We are synthesizing ligands for the in vivo transport of AEEs,119-antimony (119Sb) and 58m-cobalt (58mCo). Sister isotopes (117Sb,55Co) can be used for diagnostics.

Using our high-valent non-heme ironcomplexes we are developing a newelectrocatalytic technology for the totalmineralization of organic pollutants (e.g.pesticides) in contaminated water.

The next step is immobilization of thecatalysts of on electrode materials e.g.graphene.

PET/CT image of AR42J tumor (arrow) in mouse using a 55Co complex (right).

row) wght).

Assistant Professor Changzhu Wu

Nanobiocatalysis (1-4)

Project 1. Artificial enzymes

Project 4. Responsive bio-nanoreactors Project 3. Chemoenzymatic polymers

1). Polymeric emulsions can be used as efficient bioreactorsfor biocatalysis with easy separation.

2). A block-copolymer will be synthesized as above; it providesnot only amphiphilic structure, but catalytically active sites.

3). Upon enzyme encapsulation, the system will be applied for chemoenzymatic reactions with large-surface contact.

email: wu@sdu.dkweb: https://danish-ias.dk/events/changzhu-wu/

O

Scaffold protein Catalytic side ≡

NBoc

O

OHNH

OMe

O

+

NBoc

N

O

HO

HO

O

OH

NBoc

N

O

HO

O

OH

Cl

O+

NBoc

N

O

O

O

OH

+

O

OtBu

OtBuO

H2N

NHO

NHN

OHO

O

COOH

OO

HCl

O

NBoc

N

O

O

O

OH

O

.

.

1) EDC HCl, iPr2NEt, EtOAc

.

2) NaOH, MeOH/THF

Pyrridine

1) EDC HCl, iPr2NEt, EtOAc

2) TFA,CH2Cl2

.

TFA

Project 2. Biocatalytic biodiesel

=

Oil

Water

+1) Adsorption

or

2) Click reaction

Biocatalysis

Methanol

Decane / oil

1) 1) (CH2)17CH3

2) N3

Free enzyme

2)

SiO2E

N2 T>32oCOil

Thermal responsive pH responsive

1). Biodiesel can be produced by enzymes from oil and MeOH;

2). However, enzymes are precipitated in the solvent mixture, causing small surface contact during catalysis.

3). Here, enzymes (e.g., lipase) will be conjugated with nanoparticles, which makes enzyme amphiphilic, thus enables to emulsify the oil/MeOH two-phase into Pickering emulsions (PEs).

4) These PEs will have a larger surface area for biotransformationin biodiesel production.

1). Multiple responsive polymeric emulsions are designed, wherethermal and PH responsive polymer segments are incorporated.

2). Upon enzyme encapsulation, the system will be used for efficient biotransformation, while allowing for easy separationResponsive to CO2 (pH) and temperature.

Boosting the performance!

Looking inside a running battery

Synthesis of new electrode materials

…and characterization

Testing the battery materials

email: dbra@sdu.dk

Assistant Professor Dorthe B. RavnsbækTopics: Materials for future generation batteries

- Inorganic chemistry- Structural characterization

- Material tests

We work to achieve: • Increased energy density • Higher capacity and W • Shorter charging times • Longer lifetime • Better safety • Cheaper batteries

Li-ion batteries: We synthesis new materials for more efficient batteries and investigate how the atomic structure changes during charge and discharge.

Mg- and Al-ion batteries: The energy density can be increased by replacement of Li-ions with a multivalent ions like Mg2+ or Al3+ i) More electrons is moved per ion ii) Mg and Al metal can be used directly as

anode as opposed to Li. We develop novel cathode materials for this novelbattery technology.

Hydrothermal synthesis

Working under inert conditions

Ball milling Nanoparticles & carbon coating Sol-gel method

Nanostructured materials

Aerogel

Nanorods

Nanofibers

Nanoflowers

X-ray diffraction Phase identification & Crystal structures es

BET Particle size and morphology gy SEM and TEM

Nanotopology

• How fast can we charge and discharge the battery?• And how much charge do we get out at fast

discharge?• Does the battery loose capacity upon repeated

charge and discharge? • What is the energy efficiency of the battery

Battery stack Pellet of cathode

material

Seperator and electrolyte

Li-metal anode

Anode Separator

Cathode

• How does the structure change duringcharge and discharge?

• How does the structural change relate tothe electrochemistry?

• What is the mechanism for ion insertionand extraction?

• Is the mechanism the same during chargeand discharge?

We can measure X-ray diffraction data through a special designed test cell while the battery is running with intense X-ray radiation from a synchrotron.

We thereby obtain a “movie” of the structural changes in the electrode as they occur in real time.

Professor Ulla Gro NielsenTopics: Inorganic and Physical Chemistry

& Environmental Science

Environmental Science: Phosphate

Life in the UGN Lab and abroadpNMR and Quantum Materials

Phosphate is an environmental pollutant that causes poor water quality. Phosphate rock, a raw material for fertilizers, is considered a critical raw material by the EU.

Phosphate recovery from wastewater may cover 20% of the Danish phosphate supply.

NMR spectra of paramagnetic materials are much more complex than of an organic molecule. We study para-magnetic materials by NMR to develop a computational approach for assignment and interpretation.Collaborator: Hans J.Aa. Jensen (SDU) + Juha Vaara (Oulu)

email: ugn@sdu.dk

We understand the chemical processes in the environment by a combination of analytical chemistry and advanced characterization techniques.

Functional Materials: LDH and Clays

Collaborators: Kasper Reitzel (Biology) & Vandcenter Syd

Co(II) Ni(II) Znn(II)

Inorganic synthesis:

CharacterizationNMR spectroscopyX-ray techniquesElectron microscopyVibrational spetroscopyThermal analysesAnalytical chemistryNeutron techniques

Property tests

M(III)

M(II)

AnionControl

Mg(OH)2derived

5 Å

Catalyze

Adsorb

M(II)Al4-LDH

nm - m

Mg(OH)6

Al(OH)6

M(OH)6

Clays and layered double hydroxides (LDH) are anion-exchange materials, which can be exfoliated to form 2D materials. Our goal is to understand how the chemical structure determine their properties. We test their applications within:

Enviromental remediationDrug delivery Catalysis Energy materials

Collaborators: Carsten Uhd Nielsen, Dorthe Ravnsbæk, Christine McKenzie and industry

Classic Kagome

Ideal

b)

ppm -10000100020003000

Defect

The position of electronic spins on a crystal lattice can lead to quantum magnetic effects. We study geo-metrically frustrated antiferromagnets to link chemistry and the magnetic properties using NMR and neutrons.

Collaborator: Kim Lefmann (KU)

Tetrathiafulvalene (TTF)

Molecular Wires

Molecular Machines

Tetrathiafulvalene’s (TTF’s) Properties • Strong electron donor• Readily oxidised in a stepwise and reversible manner to TTF•+ or TTF2+, either

chemically or electrochemically• 3 oxidation states (TTF, TTF•+ and TTF2+) easily distinguished using spectroscopy• Stable under most synthetic conditions, allowing incorporation into larger

systems – see below

email: joj@sdu.dkweb: www.jojgroup.sdu.dk

Molecular Sensors –TetrakisTTF-calix[4]pyrrole

Advantages of Using TTF • tetrakisTTF-calix[4]pyrrole binds nitrated benzene derivatives (e.g.

trinitro-toluene (TNT)) – can be used to detect explosives• Distinct, easily visible colour change when TNT binds to tetrakisTTF-

calix[4]pyrrole – helpful for use in devices

Challenges • Chloride anions bind stronger than TNT to tetrakisTTF-calix[4]pyrrole and

disrupts sensing behaviour (see above)• TNT binds only to the 1,3 alternated configuration (top) – can this be

locked?

Advantages of Using TTF • TTF is an electron donor which can interact (complexate) with

cyclobis(paraquat-p-phenylene) (CBPQT4+) which is an electron acceptor• Allows preparation of interlocked systems: rotaxanes (linear) and

catenanes (cyclic)• Oxidation of TTF destroys the interaction between TTF and CBPQT4+ and

induces a movement

Challenge • Design of systems capable of using the induced movement to perform

unidirectional motion (linear or rotary)

Advantages of Using TTF • TTF’s redox properties can be used to add switching behaviour to wires• BPTTF allows for highly conjugated molecular wires – this improves

conductance

Challenges • Improve solubility of wires so conductance studies can be done• Find good anchoring groups for different electrodes (e.g. gold or

graphene)

TTF-Derivatives • Various substituents can be added to TTF to build useful molecules• Pyrrolo annelated TTFs, monopyrrolo-TTF (MPTTF) and bispyrrolo-TTF

(BPTTF), are offen used to avoid isomerism• MPTTF and BPTTF have comparable properties to TTF but different

positions to connect to other groups – this can be helpful whendesigning new molecules

Jeppesen, J. O.; Becher, J. Eur. J. Org. Chem. 2003, 3245‒3266Andersen, S. S.; Share, A. I.; Poulsen, B. L. C.; Kørner, M.; Duedal, T.; Benson, C. R.; Hansen, S. W.; Jeppesen, J. O.; Flood, A. H. J. Am. Chem. Soc. 2014, 136, 6373‒6384Nielsen, K. A.; Cho, W. S.; Jeppesen, J. O.; Lynch, V. M.; Becher, J.; Sessler, J. L. J. Am. Chem. Soc. 2004, 126, 16296‒16297Solano, M. V.; Della Pia, E. A.; Jevric, M.; Schubert, C.; Wang, X.; van der Pol, C.; Kadziola, A.; Nørgaard, K.; Guldi, D. M.; Nielsen, M. B.; Jeppesen, J. O. Chem. Eur. J. 2014, 20, 9918‒9929.

+

-

e-

Cartoon of a TTF-based molecular machine (catenane)

Professor Jan O. JeppesenTopics: Organic Chemistry, Supramolecular

Chemistry, Analytical Chemistry and Tetrathiafulvalene

Supramolecular Chemistry

Supramolecular Polymers

Organic Solar Cells

The area of Supramolecular Chemistry covers non-covalent interactions between molecules toassemble larger ordered structures. The non-covalent nature of these structures makes themhighly sensitive towards external stimuli, which canbe exploited in e.g. sensors and electron-transferprocesses.Tetrathiafulvalene is a highly electron-rich moleculethat functions as a S-electron donor. This has madeit ideal as a building block in SupramolecularChemistry and the sensing of explosives (e.g. TNT)and Buckminster fullerenes.

B. Sc. Project Jesper Tversted. Synthesis andinvestigation of extended tetrathiafulvalenereceptor for fullerene by computational modelling,NMR, absorption, ITC, CV and transientspectroscopy.

email: sbahring@sdu.dk

Assistant Professor Steffen BähringTopics: Supramolecular Chemistry and

Synthetic Organic Chemistry

Fullerene Receptor

18S

Concentration and temperature dependentpolymerization of TTF-monomers investigated byabsorption spectroscopy, NMR, AFM and DLS.

Professor  Jesper WengelSynthetic Bio‐organic Chemistry and 

Medicinal  Chemistry

Peptide‐Oligonucleotide Conjugates 

Pyrene‐Modified Unlocked Nucleic Acids

Synthesis of Novel Nucleotide Analogues

Incorporation of pyrene‐UNA monomers increasedduplex stability relative to UNA monomers, andthermodynamic studies revealed significant mismatchdiscriminative capabilities of the pyrene‐UNAmodified oligonucleotides.

Pyrene excimer emission was observed for single‐stranded oligonucleotides containing three pyrene‐UNA modifications, whereas this excimer emissiondisappeared after hybridization to DNA. These resultssuggest these derivatives as useful in diseasediagnostics.

InsertPictureHere

email: jwe@sdu.dkweb: http://www.sdu.dk//NAC

New mono‐ and diaminated 2′‐amino‐LNA monomershave been synthesized and introduced intooligonucleotides. Each modification imparts significantstabilization of nucleic acid duplexes and triplexes,excellent sequence selectivity, and significant nucleaseresistance.

Oligonucleotides Containing Aminated 2’‐Amino‐LNA Nucleotides

Kasper K. Karlsen et al. ChemBioChem (2012), 13(4), 590–601.Andreas S. Madsen and Jesper Wengel. The Journal of OrganicChemistry (2012), 77(8), 3878–3886.

Peptide‐based structures can be designed to yieldartificial proteins with specific folding patterns andfunctions. Here, we show the applicability ofpeptide–oligonucleotide conjugates for self‐assembly of higher‐ordered protein‐like structures.

First examples of the use of dioxane as sugar moiety inoligonucleotides. Thermal denaturation and circulardichroism measurements demonstrate that deoxy‐oligonucleotides containing a single incorporation ofeither monomer are capable of duplex formation withboth DNA and RNA complements. Related nucleosidesare being synthesized as potential antiviral andanticancer agents.

Chenguang Lou et al. Bioconjugate Chem., (2017), 28 (4),1214–1220

Chenguang Lou et al. Nature Commun. (2016), 7, 12294

Michael PetersenMichael�PetersenComputational studies of bacterialComputational�studies�of�bacterial�membranes and cell wall synthesismembranes�and�cell�wall�synthesis

Motivation and main objectives MethodsMotivation�and�main�objectives MethodsThe spread of infectious diseases and the increase in We employ mainly molecular dynamics calculations in antibiotic resistance represents a life-threatening our studies. From integration of Newton’s 2nd law, a global development that calls for new approaches to trajectory of a molecule’s dynamics is produced.control microorganisms. This allows study of molecular interactions and

dynamics at atomic level, which can be In this project we use computational methods to study hard/impossible to study experimentally.key components and key steps in the bacterial cell wall synthesis. Bacterial cell wall biosynthesisBacterial�cell�wall�biosynthesisWith our results we can

b id th b t th i t l t t l• bridge the gap between the experimental structurali f ti il bl f ti i bi l tid th tinformation available for antimicrobial peptides thatt t b t i l ll ll th i d th bi l i ltarget bacterial cell wall synthesis and the biologicalk l d th i d f tiknowledge on their mode of actiond t i f ti l d l f ti i bi l• determine functional models of antimicrobial

tid l i th i ti i t tpeptide complexes in their native environment atth f f l bthe surface of a plasma membrane

ibl id t t l b i f d l t• possibly provide a structural basis for developmentand design of ne antibacterial agentsand design of new antibacterial agentsincrease the understanding in key steps in the cell Figure 1 Schematic representation of cell wall biosynthesis and• increase the understanding in key steps in the cellwall synthesis

Figure 1. Schematic representation of cell wall biosynthesis and indication of antibiotic target sites in red boxes.wall synthesis g

Example�1�– Plectasin Example�2�– The�Transglycosylasep p g y yPlectasin is a fungal defensin a naturally occurring The transglycosylase is the enzyme that catalyses thePlectasin is a fungal defensin, a naturally occurring protein that exhibits antibacterial activity

The transglycosylase is the enzyme that catalyses the elongation of the glycan chain in the cell wall by linkingprotein that exhibits antibacterial activity. elongation of the glycan chain in the cell wall by linking the incoming building blocks carried by lipid II It is anthe incoming building blocks carried by lipid II. It is an attractive but relatively poorly investigated antibioticsattractive, but relatively poorly investigated, antibiotics targettarget.

Figure 2. Plectasin embedded in a S. Aureus model membrane. The defensin binds to Lipid II, carrier of cell wall building blocks.

Figure 3 The transglycosylase bound to two lipid II moleculesFrom simulations we can describe the interactions

Figure 3. The transglycosylase bound to two lipid II molecules, with linking of the sugar moieties imminent. The thickness of theFrom simulations we can describe the interactions

between the defensin and a realistic model of awith linking of the sugar moieties imminent. The thickness of the membrane is indicated and the growing glycan chain is marked between the defensin and a realistic model of a

bacterial membrane we can validate and propose newwith an arrow.

bacterial membrane, we can validate and propose new models for the defensin’s interaction with lipid II and In this project we can investigate the energetics ofmodels for the defensin s interaction with lipid II and we can propose lipid II-binding modes for other

In this project we can investigate the energetics ofglycan formation in cell wall synthesis deepen thewe can propose lipid II binding modes for other

antibiotics.glycan formation in cell wall synthesis, deepen the structural understanding of how glycan chain formationantibiotics. structural understanding of how glycan chain formation proceeds and investigate binding between theproceeds and investigate binding between the transglycosylase and possible inhibitors that can actP ibili i transglycosylase and possible inhibitors that can act as antibiotics.Possibilities as antibiotics.

Studies of interactions with bacterial membranes, Stud es o te act o s t bacte a e b a es,targeting of cell wall intermediates, investigation of

E mail: mip@sdu dkg g , g

enzymatic catalysis. EͲmail:�mip@sdu.dky y

Professor Poul Nielsen Synthetic Organic Chemistry;

DNA Modifications and Medicinal Chemistry

Double-headed nucleotides

Insert Picture Here

email: pouln@sdu.dk http://www.sdu.dk/en/Om_SDU/Institutter_centre/NAC/Research/Research_projects/Synthetic_Chemistry

Pleuromutilin – an antibiotic binding to bacterial ribosomes

A click chemistry strategy towards new pleuromutilin conjugates:

Chemical footprinting and molecular modelling:

Collaboration with Jacob Kongsted (FKF) and Birte Vester (BMB)

The best derivative

so far. Activity against MRSA

Footprints in the

active site (binding)

The binding

site in the ribosome

(PTC)

DNA therapeutics

Modelling

Synthesis

Biological tests

X-ray crystallography

Medicinal chemistry

- towards new antibioticsChloramfenicol – a well known antibiotic with side effects

New derivatives are designed based on modelling and synthesized:

Derivatives are made by simple reactions

e.g.Click chemistry,

Sonogashira coulings, and/ or

peptide couplings

Synthesis by Click Chemistry and incorporation into DNA by using a DNA-synthesizer:

BaseO

HO

OH Base

Idea: Regocnition of secondary nucleic acid structures. Designing new nucleic acid motifs. Aptamers. Development of Double-coding DNA

DNA extended

with additional base pair

DNA with an artificial

dinucleotide Synthesis:

Building block for

DNA synthesis

Blocking translation by synthetic antisense DNA

Chemical modification is necessary for improving physiological stability and RNA-affinity

Increasing the aromatic surface leads to S�S-stacking and increased RNA-affinity

Watson-Crick base-paring

Stacking in major groove

Recent ref: Pawan Kumar, Mick Hornum, Lise J. Nielsen, Gerald Enderlin, Nicolai Krog Andersen, Christophe Len, Gwénaëlle Hervé, Guillaume Sartori and Poul Nielsen,.J. Org. Chem. 2014, 79, 2854-2863

Recent refs: Pawan Kumar, Pawan K. Sharma, Charlotte S. Madsen, Michael Petersen and Poul Nielsen, ChemBioChem 2013, 14, 1072-1074. Pawan Kumar, Pawan K. Sharma and Poul Nielsen, J. Org. Chem. 2014, 79, 11534-11540.

Different designs have been approached. This one positions the additional nucleobase in the duplex core

Cu(I)

Recent refs: Ida Dreier, Surender Kumar, Helle Søndergaard, Maria Louise Rasmussen, Lykke H. Hansen, Nanna H. List, Jacob Kongsted, Birte Vester and Poul Nielsen, J. Med. Chem. 2012, 55, 2067-2077. Ida Dreier, Lykke H. Hansen, Poul Nielsen and Birte Vester, Bioorg. Med. Chem. Lett. 2014, 24, 1043–1046.

Alkynes with a variety of side chains are prepared

C R2HCR1 N3 +N N

NR1 R2[Cu(I)]

- with Click ChemistryDiversity with a simple general reaction. High yields. No side products. Possible in aqueous solution. Used intensively to link complex molecules together. Huisgen cycloaddition with Sharpless-Meldal conditions

Collaboration with Michael Petersen (FKF)

Assoc. Prof. Stefan VogelTopics:

Chemistry & Catalysis in Nanoreactors and Liposomal Drug Delivery of DNA & PeptidesLiposomal Drug Delivery of DNA & Peptides

Liposomal platform for targeted drug deliverySynthesis of Lipid building blocks for automated DNA & Peptide synthesisWe synthesize lipophilic building blocks for DNA, PNA and Peptides – and incorporate them into oligomers with therapeutic applications.

Liposomal platform for targeted drug deliveryLiposomes allow free variation of payload vs. targeting vector concentrations. Their size controls bio-distribution. Investigation for the treatment of pancreatic cancer:incorporate them into oligomers with therapeutic applications.

Membrane-anchored DNA with therapeutic activity.A specific G-Quadruplex (G4) forming sequence can inhibit KRASexpression in mammalian cell. It is called “decoy” as it scavenges animportant KRAS transcription factor (MAZ) by mimicking its naturalchromatin target.

pancreatic cancer:

G4-decoy

R = R =

X Zfor DNA-synthesis

YR =

OCH3

for PNA/Peptide synthesis

Anchor building blocks

FmocDMTr

Membrane anchored cell-penetrating peptide.Cell penetrating peptide aids uptake of the G4 into the cell.

ATAT-peptide

PO

N

N

N

RR

OO

OH3CO

O

HN R

OH

HN

OH

O

FmocDMTr

phosphor-amidite

Lipid-DNA or Lipid-PNA/Peptide conjugates

spacerspacer

spacerspacer

Design Example Sequence

DNA

PNA/

5'-end 3'-endT-X-PEG3-TGT GGA AGA AGT TGG TG

N-terminus C-terminusspacer

B

spacerspacerPNA/Peptide EE-XX-PEG12 ata gtt aca tgc EE

O

NO

NOO

NNNH2

NHNO

N

NH2

NH

O

DNA-chain PNA-chain N = Nucleobases

spacer

HOOC-EEE-XX-YGRKKRRQRRR-E-NH2

TAT-peptide

Intercalator-stabilized G4 (ODN1)5'-GCG GTG TGG GPA AGA GGG AAG APGGGG GAG GCAL GLTT X TTT-3'

Ries, O., et al., Organic & Biomolecular Chemistry 2015, 13 (37), 9673-9680; Rabe, A. et al. Chem Commun 2017, submitted. Cogoi, S., et al., Scientific Reports 2016, 6, 38468.

A) Colony formation of Panc-1 cells when treated with liposomes loaded with TAT and ODN-1, -2, or -3 (non-G4), and controls, TAT-Liposomes only (L) and untreated (NT) . B) Histogram showing the percentage of colonies

Spacer units PEG3, PEG6, PEG12 or T (DNA) / E (glutamic acid, peptide)

NH

NO

a, t, g, c

OPO O-

N

NNH

NH

NNH NH2

N

NH

O

NH

NH

O

A, T, G, C Adenine Thymine Guanine Cytosine OO

O

PO

-O

para-TINA (P)

Environmental and Health Diagnostics using Nanoparticle assembly

Programmed chemical and enzymatic reactions in liposomes

Ries, O., et al., Organic & Biomolecular Chemistry 2015, 13 (37), 9673-9680; Rabe, A. et al. Chem Commun 2017, submitted. Cogoi, S., et al., Scientific Reports 2016, 6, 38468. (L) and untreated (NT) . B) Histogram showing the percentage of colonies relative to NT.

DNA-encoded liposomes assemble into large aggregates (visible byeye). Assembly can be triggered by binding of a biological targetstrand for DNA/RNA diagnostics or toxic metals such as mercury(stabilizes T:T mismatch), or lead (stabilizes G-quadruplexes).

using Nanoparticle assembly reactions in liposomesLiposomes as reaction flasks: DNA-programmed mixing of tiny volumes.

(stabilizes T:T mismatch), or lead (stabilizes G-quadruplexes).Non-covalent attachment of lipid-DNA-conjugates to soft nano-particles, like liposomes, is an attractive technology as it needs nosurface chemistry.

Target DNA-sequence or

Hg2+

Horseraddish peroxidase (HRP)

Hg2+

orPb2+ Löffler, P. M. G., et al., Angew. Chem., Int. Ed. 2017 (DOI: 10.1002/anie.201703243); Ries, O., et al., Org. Biomol. Chem. 2017 (DOI:

10.1039/C7OB01939D)

Single Liposomes Liposome assembly

DNA/RNAdiagnostics

HPPA HRP(HPPA)2

O

O H2O2HRP

HEPES-

OH

O

OO-

O

h

Strain-Promoted Azide Akyne Cycloaddition (SPAAC, ”click-chemistry”)

diagnostics HO buffered saline(pH 7.0)

OHO

Fluorescent

email: snv@sdu.dkweb: http://biomembranes.euJakobsen, U., et al., Journal of the American Chemical Society 2008, 130 (32), 10462-10463; Jakobsen, U., et al., Bioconjugate Chemistry 2013, 24 (9), 1485-1495; Jakobsen, U., et al., Org. Biomol. Chem. 2016, 14 (29), 6985-6995.

Associate Professor Jasmin MecinovićTopics: Medicinal Chemistry, Chemical Biology,

Organic Chemistry, Bioorganic Chemistry

Chemical Basis of Epigenetics

• Aim: to unravel the chemical basis of epigenetics• Objectives: to explore posttranslational modifications of histone proteins• Approach: chemical biology and physical-organic chemistry• Techniques: synthesis, peptide chemistry, protein chemistry• References: Nat. Commun. 2015, 6, 8911, Chem. Commun. 2018, 54, 2409-2412,

Chem. Commun. 2017, 53, 13264-13267, Sci. Rep. 2017, 7, 16148.

email: mecinovic@sdu.dk

Discovery of Epigenetic Inhibitors

Carnitine Biosynthesis Organocatalysis and metalocatalysis

O

NH O

PO

O OO

NH O

PO

O O

NH O

O PO

OO

NH

NH O

N

NH O

N

NH O

O

NH O

OAcHN

OHOHOH

HN

NH O

O

HN

NH O

O

NH

H2N

NH O

NH

NH

HN

NH O

NH

NH

H2N

NH O

N

NH

O

NH O

NH2

• Aim: to develop new epigenetic inhibitors of therapeutic potential• Objectives: to design novel chemical probes for histone lysine methyltransferases• Approach: medicinal chemistry• Techniques: synthesis, inhibition assays• References: ChemMedChem 2018, 13, 1405-1413, Bioorg. Med. Chem. Lett. 2018,

28, 1234-1238.

• Aim: to investigate the human carnitine biosynthesis pathway • Objectives: to explore substrate scope of enzymes involved in carnitine biosynthesis• Approach: organic chemistry and chemical biology• Techniques: synthesis, enzymology• References: Org. Lett. 2017, 19, 400-403, Org. Biomol. Chem. 2017, 15, 1350-1354,

Chem. Commun. 2016, 52, 12849-12852, Chem. Eur. J. 2016, 22, 1270-1276.

• Aim: to develop new catalytic reactions for conversion of common functionalities• Objectives: to develop green organophosphorus and metalocatalysed reactions• Approach: organic chemistry • Techniques: synthesis, NMR• References: Green Chem. 2018, 20, 4418-4422, Org. Biomol. Chem. 2017, 15, 6426-

6432, Chem. Commun. 2014, 50, 5763-5766.

H2N

N

OH

O

H2N

HO

N

OH

O

N

O

N

OH

O

N

OH

O

HO

NH

N

O

Protein degradation TMLH

BBOX

HTML aldolase

TMABA dehydrogenase

2OGO2

succinateCO2

2OGO2

succinateCO2

NADH NAD+

trimethyllysine (TML, 1) 3-hydroxytrimethyllysine (HTML)

trimethylaminobutyraldehyde (TMABA)γ-butyrobetaine (γBB)L-carnitine (CAR)

trimethyllysine-containingprotein

R1-COOH + H2N-R2R1 N

H

OR2cat.

R1-CONHR2 + R3-CONHR4R1 N

H

OR4cat.

R1-CONH2 + H

2N-R2R1 N

H

OR2cat.

R3 NH

OR2+