Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair.
Galectins have been recognized as potential novel therapeutic targets for the numerous fundamental biological processes in which they are involved. Galectins are key players in homeostasis, and as such their expression and function are finely tuned in vivo. Thus, their modes of action are complex and remain largely unexplored, partly because of the lack of dedicated tools. We thus designed galectin inhibitors from a lactosamine core, functionalized at key C2 and C3' positions by aromatic substituents to ensure both high affinity and selectivity, and equipped with a spacer that can be modified on demand to further modulate their physico-chemical properties. As a proof-of-concept, galectin-3 was selectively targeted. The efficacy of the synthesized di-aromatic lactosamine tools was shown in cellular assays to modulate collective epithelial cell migration and to interfere with actin/cortactin localization.
Faculté des Sciences et des Techniques, Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, UMR CNRS 6286, 2 chemin de la Houssinière, B. P. 92208, 44322, Nantes Cedex 3, France.
Johann
J
Dion
Université Paris Diderot-Paris 7 Sorbonne Paris Cité, Institut Jacques Monod, UMR CNRS 7592, 15 rue Hélène Brion, 75205, Paris Cedex 13, France.
Frédérique
F
Deshayes
Faculté des Sciences et des Techniques, Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, UMR CNRS 6286, 2 chemin de la Houssinière, B. P. 92208, 44322, Nantes Cedex 3, France.
Nataliya
N
Storozhylova
Université Paris Diderot-Paris 7 Sorbonne Paris Cité, Institut Jacques Monod, UMR CNRS 7592, 15 rue Hélène Brion, 75205, Paris Cedex 13, France.
Tamara
T
Advedissian
Faculté des Sciences et des Techniques, Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, UMR CNRS 6286, 2 chemin de la Houssinière, B. P. 92208, 44322, Nantes Cedex 3, France.
Annie
A
Lambert
Université Paris Diderot-Paris 7 Sorbonne Paris Cité, Institut Jacques Monod, UMR CNRS 7592, 15 rue Hélène Brion, 75205, Paris Cedex 13, France.
Mireille
M
Viguier
Faculté des Sciences et des Techniques, Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, UMR CNRS 6286, 2 chemin de la Houssinière, B. P. 92208, 44322, Nantes Cedex 3, France.
Charles
C
Tellier
Faculté des Sciences et des Techniques, Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, UMR CNRS 6286, 2 chemin de la Houssinière, B. P. 92208, 44322, Nantes Cedex 3, France.
Christophe
C
Dussouy
Université Paris Diderot-Paris 7 Sorbonne Paris Cité, Institut Jacques Monod, UMR CNRS 7592, 15 rue Hélène Brion, 75205, Paris Cedex 13, France.
Françoise
F
Poirier
Faculté des Sciences et des Techniques, Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, UMR CNRS 6286, 2 chemin de la Houssinière, B. P. 92208, 44322, Nantes Cedex 3, France.
Cyrille
0000-0002-9775-6917
C
Grandjean
D000606:Amino Sugars / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001798:Blood Proteins; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D037483:Galectin 1 / Q000037:antagonists & inhibitors; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D037161:Galectins / Q000037:antagonists & inhibitors; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects*
D000606:Amino Sugars; D001798:Blood Proteins; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; C092525:LGALS7 protein, human; C032233:lactosamine
cell migration; drug design; galectin-3; inhibitors; skin tissue repair; wound healing