Question

A research group has experimented with a polyethylene glycol (PEG)-based tissue-engineering scaffold. This scaffold was then modified with an RGD peptide sequence. In this experiment, the RGD sequence was synthesized in one of two forms:

a) RGD coupled to a large PEG spacer (MW = 3400 Da) and attachment site moiety (***),

or

b) RGD coupled to the attachment site moiety (***) with very small PEG spacer as shown below. (MW = 800 Da).

1) Now that you know the role of the RGD terminal sequence in cell adhesion, what is the role of the PEG chain? Why did the researchers try different PEG molecular weight?

2) Based on the different designs we have seen in class for hemocompatible surfaces (e.g., Carmeda and Trillium), which form of the RGD sequence peptide will yield the highest cell attachment per given number of peptides when attached to the polymer scaffold? Justify your answer

Answer 1

1

Altering the peg chain length affects the extravasation of RGD motif to say penetrating tumours and improves the pharmacokinetic properties of RGD motif. Longer PEG chains mean that bonding to drug molecules (drug load) increases and is more effective in drug delivery process.

2.iRGD motif(9 amino acid cyclic Peptide) will yield highest cell attachment per given number of peptides as it penetrates say a tumour tissue via integrins,gets cleaved and binds to neuropilin activating an endocytic/exocytic pathway for improved extravasation.Interestingly it does not penetrate a normal tissue but can pass the drug load through a cancerous tissue.