Glycan-targeted PEGylation for selective modification of proteins

LEDERKREMER R M; AGUSTI R; GIORGI M. E

Polymer-Protein Conjugates: From Pegylation And Beyond

ELSEVIER

Lugar: Amsterdan; Año: 2019; p. 235 - 270

Pegylation of proteins is a well established procedure for improving drug delivery (?) and several conjugates are commercialized by pharmaceutical companies (capit. anteriores). However, this approach usually yields heterogeneous products due to partial or multi- conjugation to the -amino group of lysines and also to the unprotected -amino of the N-terminal aminoacid . If several lysines are present and depending on their position in the chain, active sites may be shielded or the tertiary structure of the protein altered. To overcome these shortcomings, methods for site specific aminoacid conjugation were developed (citas). One of them takes advantage of the site selective glycosylation of a protein for introduction of a pegylated carbohydrate or for pegylation of a native glycoprotein. The modification of proteins known as glycoPEGylation refers to the introduction of a PEGylated sugar to a glycan already attached to the protein. The glycan may be specifically introduced in a first step or may be present in the native glycoprotein.Other techniques that rely on PEGylation of the carbohydrate linked to a protein will be also discussed in this chapter. The application in chemotherapy of carbohydrate pegylation by itself has been reviewed (nuestras citas).