Site-Specific Polymer Attachment to a CCL-5(RANTES)Analogue by Oxime Exchange

摘要

Site-specific attachment of covalent modifiers such as polymers using chemoselective ligation chemistries is preferred over random attachment for the development of protein Pharmaceuticals.In particular,oxime-forming ligation has proven useful for the attachment of polymers to proteins or peptides since it is orthogonal to most protein functional groups and protein synthesis schemes.Oxime bonds may be formed between an aminooxy group,such as aminooxyacetic acid(Aoaa),and an aldehyde or ketone functionality,such as glyoxylic,levulinic,or pyruvic acid.We have developed an improved synthetic strategy that allows effective protection of the aminooxy group during peptide synthesis,peptide ligation,and protein folding.