Dynamic combinatorial chemistry (DCC) and the well-known concept of enhanced binding to lectin surfaces by multivalent presentation of sugar subunits[1] have been combined to better understanding the principles governing carbohydrate recognition. Analysis of the lectin binding properties of a metal based multivalent dynamic combinatorial library (DCL) that can reversibly exchange its binding entities by multiple (more than two) connecting points is unprecedented.[2] Coordination of bipyridine type ligands around a metal centre was selected as the reversible interaction for multivalent exchange. The concept and feasibility of this approach were first established by coordination of a library of different non sugar containing ligands around CoIIand FeII.[3] LC-MS analysis was employed to detect all possible structures resulting from the intermolecular exchange process. Then, three different carbohydrate containing ligands were synthesized; sugars of different mass and affinity to the target lectin were selected. The complexes were prepared to set-up a 10 member metal based self-assembling adaptive library, which then was analysed by LC-MS. The binding properties of the mixture to a lectin surface were screened by a filtration process using a solid phase supported concanavalin A. Analysis (filtration‑LC‑MS) of the bound species clearly showed the expected bias towards the entities exhibiting a multivalent presentation of sugars with strong interactions to the protein surface.This opens a new strategy to study carbohydrate-protein interactions and to develop unusual and more selective ligands.
[1] Jayamaran, N.;Chem. Soc. Rev.,2009,38, 3463.
[2] Sanders, J. K. M.; Otto S.
; Chem. Rev.,2006,106, 3652.
[3] Goral V.; Nelen M.I.; Eliseev A.V.; Lehn J-M.;Proc. Natl. Acad. Sci USA,2001,98, 1347.
