Abstract
Combinatorial (glyco)peptide libraries offer the possibility to define effective inhibitors of protein (lectin)–
glycan interactions. If a (glyco)peptide surpasses the inhibitory potency of the free sugar, then the
new peptide–lectin contacts underlying the affinity enhancement may guide further rational drug design.
Focusing on the adhesion/growth regulatory human galectins 1 and 3, a screening of three combinatorial
solid-phase (glyco)peptide libraries, containing Gal(b1-O)Thr, Gal(b1-S)Cys/Gal(b1-N)Asn, and Lac(b1-
O)Thr, with the fluorescently labeled lectins had led to a series of lead compounds. To define the
inhibitory potency of a selection of resynthesized (glyco)peptides systematically, a surface plasmon
resonance-based inhibition assay with immobilized asialofetuin was set up. (Glyco)Peptides with up to
66-fold potency relative to free lactose as inhibitor were characterized. The presence of lactose in the
most effective glycopeptides indicated the presence of affinity-enhancing peptide–lectin contacts. In
addition to drug design, they may be helpful for fine-structural analysis of the binding sites.
| Original language | Undefined/Unknown |
|---|---|
| Pages (from-to) | 190-196 |
| Number of pages | 7 |
| Journal | Analytical Biochemistry |
| Volume | 378 |
| Issue number | 2 |
| Publication status | Published - 2008 |