Los días 8 y 9 de octubre de 2014, la Fundación Ramón Areces acogió el Simposio Internacional 'Química: respuestas para una vida mejor', organizado en colaboración con la Fundación General CSIC. Su finalidad fue ofrecer a los participantes una visión atractiva de la química moderna que sirva de base al desarrollo de nuevas respuestas para una sociedad en rápida evolución.

1. NMR AND MOLECULAR RECOGNITION. PROTEIN-CARBOHYDRATE INTERACTIONS
JESUS JIMENEZ-BARBERO
Chemical and Physical Biology
jjbarbero@cib.csic.es
jjbarbero@cicbiogune.es
MADRID
LILLY SYMPOSIUM
October 8, 2014

2. The sugar code: the recognition of carbohydrates by specific
proteins translates sugar-encoded information into cellular
responses
Gabius HJ, André S, Jiménez-Barbero J, Romero A, Solís D. Trends Biochem Sci. 2011, 36:298-
313
Solís D, Bovin NV, Davis AP, Jiménez-Barbero J, Romero A, Roy R, Smetana K Jr, Gabius HJ.
Biochim Biophys Acta. 2014, pii: S0304-4165(14)00120-2. doi: 10.1016/j.bbagen.2014.03.016

3. From NRDD (2004)
1 LIGAND STRUCTURE?
2 RECEPTOR STRUCTURE?
Complexity and
Flexibility
Soluble with
MW<X0.000

4. FROM THE PERSPECTIVE OF THE RECEPTOR:
1 LIGAND STRUCTURE?
2 RECEPTOR STRUCTURE?
Complexity and
Flexibility
Soluble with
MW<X0.000
HSQC and CHEMICAL SHIFT PERTURBATIONS

5. K16
M17
K19
N28
1H (ppm)
15N (ppm)
E15
K19
K16 M17
E18
N28
D2 FGFR
Control
Prot 1:0.25 lig
Prot 1:0.5 lig
Prot 1:1 lig
Prot 1:1.5 lig
Prot 1:2 lig
N28
L71
S70
E18
K16
N13
E15
M17
K19
FIBROBLAST GROWTH FACTORS
Fast dissociation: FGFR/HEPARIN
A. Canales, L. Nieto
2nd Partner
JACS 2006, J Biomol NMR 2006, Febs J 2006,
JACS 2008, Chem Eur J 2011 & ChemBioChem 2013

6. The ligand’s perspective:
Saturation Transfer Difference. STD (Meyer and Mayer, Peters, 1999, 2000)
IS THERE ANY BINDING FOR ANY GIVEN COMPOUND?
WHICH IS THE BINDING EPITOPE?
IRRADIATION
at the aromatic
or aliphatic
NMR regions
At long irradiation times, the saturation is transferred to the bound ligand, first
to the protons belonging to the ligand epitope, then to the rest of the ligand
Single Compound or
Library

7. 170x scale
The ligand’s perspective:
Forsmann Disaccharide/h-gal9
GalNAca1-3GalNAcbOR
i)
ii)
H1’
H2’
H4β
H4’
linker
H5
Me
Me’
linker linker
Joao Ribeiro
A.Romero, MJ Maté, HJ Gabius, D. Solís
Int J Biochem Cell Biol, 2010

8. Ligand NMR
based
methods
STD
tr-NOESY
Computational
methods
Docking
MD
CORCEMA-ST
+
tr-N STD (epitope) OESY (bound conformer)
3D structure
docking
MD
Nat Prod Rep 2011, 28, 1118-1125 , Med Chem Commun, 2014, 5, 1280-1289

9. Tubulin as chemotherapeutic target (with JF Díaz & JM Andreu)
a-tubulin
b-tubulin
α,β-tubulin/taxol
(EC, PDB code 1JFF), 2001
Docetaxel
Taxol
Epothilone A Epothilone B
Dictyostatin Discodermolide
taxol
Taxol
Epothilone A Epothilone B
Docetaxel
Microtubule stabilizing agents (MSAs)
J Am Chem Soc. 2006
ACS Chem Biol. 2013
& Bacterial Tubulin (FtsZ)
J Am Chem Soc. 2013
Paclitaxel (Taxol ®)
Biophys J. 2011
Docetaxel (Taxotere ®)
ACS Chem Biol. 2011
Epothilone A
ACS Chem Biol, 2014 Epothilone B
Dictyostatin, Chem. Eur. J., 2008 Discodermolide, Chem Biol, 2012

10. HNK 1 epitope – mAntibody (Guillem-Barré Syndrome)
With N. Nifantev (Moscow), M. Schachner (Hamburg)
STD spectrum
reference
TTOOCCSSYY SSTTDD--TTOOCCSSYY
J Am Chem Soc., 2012 ;134:426-
35

11. Protein 1H
Ligand 19F
Ligands:
Simple fluorinated carbohydrates: Man, Glc, 2FDG, 3FDG
Receptors: ConA, LCA and PSA
Methodology: Proof-of-principle
Chem Eur J 2009 & Eur. J. Org. Chem. 2012 & Submitted
J. P. Ribeiro, T. Diercks (CIC Biogune)
K. El Biari
Perturb Protons at
the protein
Observe Fluorine at
the ligand
With H.J.Gabius
D. Solís
The ligand’s perspective:

12. conA + 2FDG HF STD
32x
scale
The ligand’s perspective:
Off resonance (phase mod 180º)
STD

13. 100
80
60
40
20
0
fractional STDreF [%]
Following interactions by 19F NMR.
0 5 10 15 20
inhibitor concentration [mM]
Competition experiments
19 F NMR fluorinated ligand (spy)
Addition of other possible ligands
+ ligands
H.-J. Gabius
R. Roy
T. Diercks
Chem Eur J 2009
& Eur J Org Chem 2012 & submitted
The ligand’s perspective:

14. The interactions
• Model systems: Small ligands, small proteins

15. The receptor’s perspective:
NMR Solution Structure of Hevein and their molecular complexes with chitin oligomers
The first solution state lectin-oligosaccharide complex by NMR…… (1995-2014….)
W23 W23
W21
S19 Y30
Y30 N
C
Exposed site
Preorganized
Enthalpy driven
Hydrogen bonds
Van der Waals
CH-p (Acc Chem Res, 2013)

16. The receptor’s perspective:
Binding Properties of hevein-like aromatic mutants with Chitotriose
Similar Binding Mode
Phe18
Enthalpy driven
Ka298K [M-1] DH [KJ/mol]DS[J/molK]
[KJ/molK]
Ac-AMP2 Nal18 3500 -63.9 -146.6
Ac-AMP2 W18 1700 -54.1 -119.0
Ac-AMP2 F18 1200 -50.1 -109.0
Y27
Y20
Trp18
Nal18
Dr. Muraki, Tsukuba, Ac-AMP2
enthalpy-entropy compensation

17. CH-p sugar/aromatic interactions take place in water even for
simple monosaccharide/aromatic systems
M C Fernández-Alonso, G Cuevas
Dispersion, electrostatic, hydrophobic
J. Am. Chem. Soc. 2005, 7379
Critical points Accounts Chem Res 2013
(AIM)

18. D.Díaz, K. Ramírez, C. Fernández-Alonso, G. Cuevas
Dispersion, electrostatic, hydrophobic
J. Am. Chem. Soc. 2005
Pure Appl Chem, 2008,
Aromatic aminoacids, Chem Eur J 2008
Protected sugars, J. Am. Chem. Soc, 2009
Reactivity (Dynamic Combinatorial Chemistry), J. Am. Chem. Soc, 2013
OVERVIEW: Acc. Chem. Res, 2013,

19. The ligand’s perspective:
19F NMR: WGA/chitin interactions (with N. Reichardt, CIC biomaGUNE)
19 F NMR, FREE AND BOUND
2 1
1H NMR, FREE AND BOUND
1H spectrum of ligand 2
19F NMR STD (submitted)

20. The interactions
• Increasing complexity. Larger systems

21. FIBROBLAST GROWTH FACTORS AND THEIR INTERACTIONS:
HEPARIN, HEPARAN SULFATE, AND FGFR
-Cell proliferation
-Differentiation
-Angiogenesis
-Wound healing
ANGIOGENESIS
FGFR
cis
membrane
FGFR
Signalling
autophosphorylation
Extracellular
matrix
citoplasm
heparin
FGF1
HS
trans
FIBROBLAST GROWTH FACTORS
It is known that in FGF activation:
• heparin
• specific trasmembrane receptors (FGFRs)
A. Canales, L. Nieto
M. Martin-Lomas, P. Nieto, J. Angulo (Seville)
G. Gimenez-Gallego, I. Fernández (Madrid)
Both the ligand’s and receptor’s perspective:

22. asymmetric structure symmetric structure
FGF1
FGF1-FGFR2-heparin
2:2:1
Pellegrini et al.
Nature 2000, 407, 1029-1034
TRANS: ASYMMETRIC
heparin
FGF2-FGFR1-heparin
2:2:2
Schlessinger et al.
Mol.Cell 2000, 6, 743-750
CIS: SYMMETRIC
FGFR2
FGFR2
heparin
X-RAY STRUCTURES
Ig2
Ig3 Ig3
Ig2
FGF2
FGFR1
FIBROBLAST GROWTH FACTORS

23. L145
FGF1 residues
affected by the
addition of FGFR-Ig2
that are not involved
in protein-protein
interactions in this
structure
1st Partner 2nd Partner
Protein-protein
interaction
surfaces
asymmetric
model
Y108
D102
FGF1/ FGFR-Ig2 secondary binding site
+ +
15N FGF1 unlabelled
FGFR Ig2
pentasaccharide
15N FGF1 + pentasaccharide (1:2)
15N FGF1+ pentasaccharide + FGFR Ig2 (1:2:0.25)
G140
E104
L145
E56
F53
V104
L147
M149
L21
E105
Y139E104 G140
Protein-protein
interaction
surfaces
symmetric
model
15N-1H HSQC
L28
L147
E104
G140
Y108
F36
TERNARY COMPLEX INTERACTIONS: from the FGF1 viewpoint
TERNARY COMPLEX INTERACTIONS:
Only the symmetryc complex explains all the NMR experimental observations
FIBROBLAST GROWTH FACTORS
JACS 2006, J Biomol NMR 2006, Febs J 2006, JACS 2008, Chem Eur J 2011 & ChemBioChem
2013

24. The Sugar: The bound
conformation
13C-double filtered-NOESY
CHAIR-BOAT EQUILIBRIUM
IN THE BOUND STATE!
Conformational dynamics (ligand
plasticity) is essential for
bioactivity
FGF, JACS, 2005;
5.05.105.205.305.405.05.105.205.305.403.03.504.04.50
OH
H1I5
H5
H5
H2
NH
H2
H1I1
H3,4
H3
H4
H1G6
¯
H1G2
¯
H1G4
H1I3
H2
H4
H3
H5
H2
H4
H2,3
H3,4
H2,5
H4
H3
OH
OH
HG6
1HG2
¯ 1¯
HI3
1H1I5
H1G4
HO
O
O
NH
HO
O
-O3SO
O
-OOC
O
O
HO
OH
OSO3
-
H H
H
H
H H
H
H
H
O
OH
HO
O
H
-OOC
O
O
NH
HO
H
H
H H
H
H
H H
O
-O3SO
O
-OOC
H
H
H
H
H
iPr
SO3
-
Ac
SO3
-
GlcN-6 IdoA-5 GlcN-4 IdoA-3 GlcN-2 IdoA-1
H1I5-H6G4
A B
10 .0 7.5 5.0 2.5 0.0
0.0
2.5
5.0
7.5
10.0
0
FGFR, Chem Eur J, 2011 & ChemBioChem, 2013
A. Canales, L. Nieto
First Partner

25. Mimicking conformational plasticity: The use of fluorine-containing glycans
With M. Sollogoub (UPMC, Paris)
19F-NMR spectra, RT
Idose-like (1, 3, 5, 6) & Glc-like (2, 4, 7)
________________________________________________________________
19F-NMR spectra, VT
INCREASING TEMP, DECREASING TEMP

26. Mimicking conformational plasticity: The use of fluorine-containing glycans
With M. Sollogoub (UPMC, Paris)
The Ido-like fluoro-saccharides also mimic the dynamic behavior of natural sugars!
Regular carbasugars display one unique (4C1 chair) conformation (Widmalm, 2010)!
_______________________________________________________________
________________________________________________________________
4 2S C1 5a
Luca Unione, with S. Martín-Santamaría (computations), submitted

27. Mimicking conformational behaviour: The use of fluorine-containing glycans
With M. Sollogoub (UPMC, Paris)
Gem-difluoro-sugars also mimic the dynamic behavior of disaccharides around the glycosidic linkage
________________________________________________________________
s*C1-C5a
s*C1-C2 s*C1-C2
s*C1-C2
s*C1-O1
F
F
O O O
s*C1-CF2
R
O
O R
O R
O R
O
R
R
F
F
Glycoside Carbasugar gem-diF-carbasugar
Exo
Non Exo
HO
HOH
O
OH
HOO O
HO
HO OMe
HO F
F
The exo-anomeric effect governs
the conformational behavior of
glycans around the glycosidic linkage
C-glycosyl
Asensio et al. JACS 1999, Chem Eur J 2000
________________________________________________________________
________________________________________________________________
Luca Unione, with S. Martín-Santamaría (computations), Angew Chem Int Ed Engl. 2014 ;53:9597

28. Mimicking conformational behaviour: The use of fluorine-containing glycans
With M. Sollogoub (UPMC, Paris)
Gem-difluoro-sugars also mimic the dynamic behavior of disaccharides around the glycosidic linkage
________________________________________________________________
The Gem-difluoro-maltose analogue displays the natural exo-anomeric conformation
The carbasugar analogue shows a major equilibrium around the glycosidic torsions
________________________________________________________________
Luca Unione, with S. Martín-Santamaría (computations), Angew Chem Int Ed Engl. 2014; 53:9597

29. GGllyyccaannss iinn NNaattuurree
Asn
n
N-glycans - lectins
Lys-Val-Ala-Asn-Lys-
Thr
Neu5Ac
Gal
Man
GlcNAc
Ana Ardá & Pilar Blasco
From simple molecules with single epitopes to complex molecules
with multiple epitopes
The importance of lectin architecture
The importance of single or multi domain protein domains

30. Glycopeptide binding: beyond binary complexes
A. Ardá, J. J. Hernández-Gay
Chem Eur J (2010), 16, 10715
with C. Unverzagt & HJ Gabius

31. BIANTENNARY N-GLYCANS: MULTIPLE EPITOPES!
NATURAL BIANTENNARY
OLIGOSACCHARIDES: NO
HEVEIN BINDING BY
with C. Unverzagt (Bayreuth) & HJ Gabius (München) STD!!!!

32. BIANTENNARY N-GLYCANS AND MULTIDOMAIN LECTINS: WGA, a dimer of 4 HEVEINS
THERE IS BINDING!
But…
The sialyl residues do not
contribute
to the binding event…..
Although WGA has been considered
a
Sialic acid binding protein!
MACROSCOPIC STUDIES ONLY PROVIDE PARTIAL ANSWERS!

33. NATURAL BIANTENNARY OLIGOSACCHARIDES AND LARGE LECTINS: WGA (8 HEVEINS)
With C. Unverzagt, H.-J. Gabius
A. Ardá, P. Blasco
MACROSCOPIC STUDIES ONLY PROVIDE PARTIAL ANSWERS!
J. Am. Chem. Soc . (2013)

34. To finish:
Conformation and Recognition. N-Glycans
Few key NOEs and long range Js, not easy to get.
Why not trying additional tools?

35. from G. Otting, Annu. Rev. Biophys . 2010, 39, 387–405
O
HO O
HO
OH
HN
HN
O
HO
OH
HN
CO2H
N
N
CO2H
CO2H
CO2H
O
HN
O O
O
Paramagnetic probes: Lanthanides

36. Using other NMR parameters. THE USE OF LANTHANIDES: PCS and PRE
Carbohydrate probe design
O
6´
4´ 5´
HO O
4 5
HO
OH
HN
HN
O
HO
OH
HN
CO2H
N
N
CO2H
CO2H
CO2H
O
HN
O O
O
2 1
3
6
1´
3´ 2´
A. Canales, A. Mallagaray, J. Pérez-Castells
O
6´
4´ 5´
HO O
6
4 5
HO
OH
HN
HN
O
HO
OH
HN
CO2H
N
N
CO2H
CO2H
CO2H
O O
O
1´ 1
3´ 2´
3 2
b- aminochitobiose derivatives
A. Canales, A. Mallagaray, Chem. Commun, 2011, 47(25), 7179-81
Lactose derivative
JACS (2014)

37. THE USE OF LANTHANIDES: DISACCHARIDE CONFORMATION
H1
Lactose derivative
La+3 complex
Dy+3 complex
2
1,8
1,6
1,4
1,2
1
0,8
0,6
0,4
0,2
0
0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 1,8 2
1,0
0,5
Dd = +1.78
Mspin calculation
1H PCS exp
1H PCS calc
Qfactor= 0.006
1H-13C HSQC
Dy+3
1,0
0,5
A. Canales, A. Berbís, SYNTHESIS: A. Mallagaray, J. Pérez-Castells
0,0
0,0
H5' H4' H3' H2' H1' H5 H4 H3 H2 H1
1H PCS
ppm
PCS H4´
0.27 ppm
d (H4´-Dy3+) = 20.1 Å
J.Am.Chem.Soc. 2014, 136, 8011-7

38. h-Galectin 3 binding studies (HJ Gabius, München)
Orange residues disappear due to PRE
Green residues shift d(Dy-HN S237) 31 Å
VII GERMN Biennial meeting
G235
E165
W181
S237
D178
1H-15N HSQC
Gal-3 + lactose derivative + La3+
Gal-3 + lactose derivative + Dy3+
G235
E165
W181
S237
D178
Dy3+
0.05 ppm
J.Am.A. Canales, A. Berbís, SYNTHESIS: A. Mallagaray, J. Pérez-Castells Chem.Soc. 2014, 136(22), 8011-7

39. Complex type N-glycans
-Folding control.
-Cell adhesion.
-Inmune response.
isochronous NMR shifts
N-glycans pseudosymmetry
Complex type
Gal GlcNAc aMan
H2 GlcNAc
(A+B)
H4 Gal
(A+B)
H4 aMan
(A+B)
H4 GlcNAc
(A+B)
H2 Gal
(A+B)
H5 GlcNAc
(A+B)
d (13C) ppm
d (1H) ppm
Ln3+ = La3+
1H-13C HSQC

40. Breaking pseudosymmetry in complex N-glycans with paramagnetic lanthanides and PCS
PCS 0.10 ppm
B
H2 GlcNAc
(A+B)
B
0,5
0,5
Gal GlcNAc aMan
A B
GlcNAc
aMan
bMan
Gal GlcNAc aMan
H2 bMan
H4 Gal A
(A+B)
H4 GlcNAc
(A+B)
A
0,5
B
H4 aMan
(A+B)
A B
B
H3 bMan
Gal
H2 aMan B PCS 0.41 ppm
PCS 0.29 ppm
H2 Gal
(A+B)
0,5
0,5
A B
H5 GlcNAc
(A+B)
A B
A
d (1H) ppm d (13C) ppm
A
1H PCS
ppm
0,0
H5 H4 H3 H2 H1
0,0
H5 H4 H3 H2 H1
0,0
H5 H4 H3 H2 H1
1H PCS
ppm
0,5
0,0
H5 H4 H3 H2 H1
0,0
H5 H4 H3 H2 H1
0,0
H5 H4 H3 H2 H1
1H-13C HSQC
N-glycan derivative + Dy3+
N-glycan derivative + La3+
A. Canales, with C. Unverzagt and I. Boos Angew Chem. Int. Ed. 2013, 52, 13789

41. 1,2
1
0,8
0,6
0,4
0,2
0
0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1
Green gg 180
Red gt 180
1-3 branch
1H PCSs exp
1H PCSs calc
A. Canales, with C. Unverzagt & I Boos Angew Chem Int Ed, 2013

42. Gal GlcNAc B
h-Galectin 3 binding studies. Impossible in the diamagnetic sample
1H-13C HSQC nonasaccharide + 1H-13C HSQC nonasaccharide + + hGal3
H1GalA H1GalB H1GalA H1GalB
H1GlcNAcA H1GlcNAcB H1GlcNAcA H1GlcNAcB
HSQC rows GalB
H4GalA H4GalB
4 H3GlcNAcA H3GlcNAcB
H1GalA H1GalB
H3bMan3
GlcNAcB
GalAGlcNAcA
Angew Chem. Int. Ed. 2013, 52, 13789-93
A
B
A
CR_D_ _h_G_a_l_e_c_ti_n_-3________________________________________________________

43. Further challenge: Tetraantennary N-glycan
1H-13C HSQC La3+
1H-13C HSQC Dy3+
H1 aManC H1 GlcNAc
H1 Gal
A-D
H1 aManA
A+C
H1 GlcNAc
B+D
A C
D B
A D B C
H1 bMan
H1 GlcNAc2
D
C
B
A 3 2 1
The chemical shifts of the four Galactose moieties are isochronous
The chemical shifts of the four GlcNAc units are isochronous in pairs (A, C & B, D)

44. Overall fitting A, B, C and D arms
gg_gt/gg_gg 60/40 Qf 0.16 single tensor
R2 = 0,9459
1,400
1,200
1,000
0,800
0,600
0,400
0,200
gg_gt PCS (Exp, calc)
H1 GlcNAc C (0.4, 0.46)
H2 GlcNAc C (0.38, 0.31)
H3 GlcNAc C (0.42, 0.42)
H5 GlcNAc C (0.44,0.45)
H1 Mana 1-6 (0.43, 0.43)
H1 GlcNAc A
(0.18, 0.12)
H1 GlcNAc B
(0.29, 0.22)
H1 Gal C (0.28, 0.27)
C
D
A
B What about the interaction with a
receptor?
A. Canales, with C. Unverzagt & I. Boos
submitted
0,000
0,000 0,200 0,400 0,600 0,800 1,000 1,200 1,400

45. Line broadening upon addition of h-galectin3 HSQC rows
H4 GalA H4 GalD H4 GalB H4 GalC
% intensity
respect to the
sample without
protein
89% 56% 33% 34%
HSQC 1H-13C tetraantennary N-glycan +Dy3+ HSQC 1H-13C tetraantennary N-glycan +Dy3+ +gal3, Molar ratio 12:1
H2 GalA H2 GalD H2 GalB
76%
55% 44%
H2 GalC
46%
B
A
C
D
B and C arms are more affected, followed by arm D
Branch A is basically non-accesible to hGal3
A. Canales, with C. Unverzagt & I. Boos
submitted

46. B
A
C
D
A and D arms are less
accessible to potential
binders than C and B
Paramagnetic lanthanides:
Breaking pseudosymmetry and unraveling “hidden” molecular recognition features
19F-containing glycomimetics:
Mimicking conformational behavior and plasticity
Unraveling the key role of carbohydrate-aromatic interactions for sugar recognition
Applications of NMR techniques for addressing molecular recognition events,
from the ligand (1H and 19F) and receptor’s perspective

47. J. Jiménez-Barbero, F. J. Cañada
CIB-CSIC, Madrid, SPAIN
FORMER MEMBERS
J. L. Asensio (IQOG)
J. F. Espinosa, A Rivera
P Vidal, L Calle (Lilly)
A. Poveda (UAM)
M. Martín-Pastor (USC)
J. I. Santos (UPV-SS)
F. Corzana (La Rioja)
J. Pérez-Castells, CEU
N. Aboitiz (Army)
E. Montero (UK)
P. Groves, F. Marcelo (Lisbon)
S. Mari (Milano)
M. Fontanella (Padova)
C. Venturi (Florence)
V. Gargiulo, C de Castro
R Marchetti (Napoli)
M. Politi (Genoa)
G. Cuevas, M. I. Chavez, M Morando
B. Domínguez, K. Ramírez (UNAM)
V. García-Aparicio, J. J. Hdez-Gay
A. García-Herrero (Canada)
K. Martínez-Mayorga, JL Medina (Florida)
J. Ribeiro (Grenoble)
L. Nieto (Eindhoven)
V. Roldós (Montevideo)
A. Mallagaray (Luebeck)
LANTHANIDES
C. Unverzagt (Bayreuth)
J. Pérez-Castells (USP-CEU)
HML, Galectins
H.-J. Gabius (München)
S-I. Nishimura (Sapporo)
Heparin/FGF/FGFR
M. Martín-Lomas (BMG)
G. Giménez-Gallego (CIB)
P.M. Nieto (IIQ)
R. J. Linhardt (NY)
Hevein, Chitin
A. Rdgez-Romero (UNAM)
G. Asensio (Valencia)
D. Andreu (Barcelona)
M. Vila (Barcelona)
M. Muraki (Tsukuba)
€
•MINECO (Spain)
•CAM (Madrid)
•FP6, FP7, H2020 (EU):
•GlycoHit
•Dynano
•Glycopharm
•TOLLerant
•COST BM1003, CM1102
•Mizutani
•Cariplo
•Pharmamar, Rovi, Vertex,
ImmunoTek, Syngenta
•Marató TV3
•CSIC (PIF)
CIB-CSIC (2014)
Ana Ardá
Angeles Canales
Ana Manzano
Carmen Fernández-Alonso
Alberto Fernández-Tejada
Dolores Díaz
Pilar Blasco
Khouzaima El Biari
Alvaro Berbís
Luca Unione
Javier Sastre
Silvia Galante
Beatriz Fernández de Toro
Modeling
S. Martín-Santamaría
(USP-CEU, Madrid)
NMR (800 MHz)
M. Bruix (IQFR)