Site-specific polymer attachment to a CCL-5 (RANTES) analogue by oxime exchange.

Autor: Shao H; Gryphon Therapeutics, 600 Gateway Boulevard, South San Francisco, CA 94080, USA., Crnogorac MM, Kong T, Chen SY, Williams JM, Tack JM, Gueriguian V, Cagle EN, Carnevali M, Tumelty D, Paliard X, Miranda LP, Bradburne JA, Kochendoerfer GG
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2005 Feb 09; Vol. 127 (5), pp. 1350-1.
DOI: 10.1021/ja043096w
Abstrakt: A synthetic strategy that allows for the site-specific attachment of polymers such as poly(ethylene glycol) (PEG) to protein pharmaceuticals is described. PEG was attached to a 67-amino acid fully synthetic CCL-5 (RANTES) analogue at its GAG binding site both to reduce aggregation and to increase the circulating lifetime. Effective protection of an Aoaa chemoselective linker during peptide assembly, total chemical protein synthesis, and protein folding was achieved with an isopropylidene group. Mild deprotection of the resulting folded synthetic protein and subsequent polymer attachment occur without interference with the native folded structure and activity.
Databáze: MEDLINE