Proteins site-specific conjugation

The preparation of polymer-protein conjugates is possible by two mechanisms random and site-specific conjugation. In the case of random conjugation, the polymer is usually linked to lysine groups of the proteins. Site-specific conjugation, on the other hand, is based on the insertion of cysteine residues with exposed thiol groups which react preferentially with vinyl or vinyl sulfon groups of the smart polymers (Hoffman and Stayton, 2007). 

Zhang Y, So MK, Loening AM, Yao H, Gambhir SS, Rao J. (2006) HaloTag protein-mediated site-specific conjugation of bio-luminescent proteins to quantum dots Anp/ew Chem IntEd En l 45, 4936-4940. 

Cysteine-Containing Fusion Tag for Site-Specific Conjugation of Therapeutic and Imaging Agents to Targeting Proteins... 

Fig. 1. Conjugation of the payload to a protein for targeted delivery. (A) Random conjugation results in a heterogeneous mixture of products. (B) Site-specific conjugation to Cys-tagged proteins leads to functionally active uniform products.

Chilkoti A, Chen G, Stayton PS, Hoffman AS. Site-specific conjugation of a temperature-sensitive polymer to a genetically-engineered protein. Bioconj Chem 1994 5 504-507. 

Lin CW, Ting AY (2006) Transglutaminase-catalyzed site-specific conjugation of small-molecule probes to proteins in vitro and on the surface of living cells. J Am Chem Soc 128 4542- 543... 

A special group of carrier-linked prodrugs are the site-specific chemical delivery systems [23], Macromolecular prodrugs are synthetic conjugates of drugs covalently bound (either directly or via a spacer) to proteins, polypeptides, polysaccharides, and other biodegradable polymers [24],... 

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