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Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Heterobifunctional ligands: practical chemoenzymatic synthesis of a cell adhesive glycopeptide that interacts with
M Matsuda1, S Nishimura, F Nakajima
1Division of Immunoregulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Abstract:
An efficient and practical synthesis of cell adhesive glycopeptides exhibiting unique properties as a novel type of modulator of cellular recognition is described. A nonnatural glycopeptide 1 composed of sialyl Lewis x and Lys-Gly-Arg-Gly-Asp-Ser that interacts with both selectins and integrins has been systematically synthesized by combined chemical and enzymatic strategy. It is suggested that glycopeptide 1 showed much higher affinity with P-selectin (K(a) = 6.6 x 10(7) M(-1)) and E-selectin (K(a) = 4.5 x 10(5) M(-1)) than sialyl Lewis x. This compound also inhibited a specific interaction between human integrin beta(1) and its monoclonal antibody more effectively than the tetrapeptide Arg-Gly-Asp-Ser. Interestingly, it was demonstrated by surface plasmon resonance analysis that this heterobifunctional glycopeptide exhibited a capacity to form stable complexes with P-selectin and integrin beta(1) concurrently. It is also suggested that this activity can be used for the inhibition of integrin-mediated adhesion of activated helper T cells onto collagen-coated plates as a cell migration model. These results indicate that the chemoenzymatic hybridization strategy of different biological functions of carbohydrates and peptides is a new concept for designing potent glycoconjugates as antiinflammatory and anticancer metastasis reagents.
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