Natural glycoproteins often contain heterogeneous oligosaccharide chains, which make it difficult to elucidate the structure–activity relationship of the carbohydrates of these glycoproteins. Neoglycoproteins were developed to overcome such a problem. Neoglycoproteins are proteins modified with carbohydrates of defined structures. The modification can be random or specific and can use chemical or enzymatic methods. The protein functional groups most often used are α/ɛ‐amino groups, β/γ‐carboxyl groups, γ‐carboxylamides, sulfhydrils, and phenols. In some cases, existing glycans on glycoproteins can be modified to make the glycan structures homogeneous. Alternatively, glycopeptides or glycoproteins can be synthesized totally
de novo
, without using any natural proteins, peptides, or oligosaccharides. In addition to providing homogeneous carbohydrate structures on a single protein, neoglycoproteins also provide a multivalency effect (glycoside clustering effect). The use of neoglycoproteins greatly promoted the understanding of the roles of carbohydrates in biologic systems, which led to some clinically important development.