engleski

DISULFIDE BOND FORMED BY CYSTEINES WITHIN RGD4C MOTIF INSERTED IN THE HI LOOP OF ADENOVIRUS TYPE 5 FIBER PROTEIN INFLUENCES ITS RETARGETING POTENTIAL

Absence of coxsackie-adenovirus receptor (CAR) on the cell surface, or its suboptimal localization, markedly impedes adenovirus type 5 (Ad5) infection. One of the possible approaches to solve this obstacle is adenovirus retargeting by incorporation of retargeting motifs in the HI-loop of the Ad5 fiber protein. Among others, RGD4C, an αv-integrin binding motif that enhanced infection of a wide range of tumor cells in vitro and in vivo, has been used most extensively. The RGD4C peptide contains two pairs of cysteine residues (CDCRGDCFC), introduced in an attempt to stabilize the sequence via formation of disulfide bond/s. An RGD motif without cysteines (MNDHAIRRGDTFATTRAE) is naturally present within the penton base of wild type Ad5. In the literature, both RGD containing motifs, potentially cyclic or linear, have been inserted into the HI loop of Ad5 fiber protein, resulting in enhancement of adenovirus-mediated transduction. However, up until now no one has compared their retargeting potential, nor investigated whether and how cysteines influence the retargeting potential of Ad5RGD4C.

adenovirus; gene therapy; ratergeting; RGD

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