Identification of a peptide sequence that improves transport of macromolecules across the intestinal mucosal barrier targeting goblet cells

School of Agricultural Biotechnology, Seoul National University, San 56-1, Sillimdong, Gwanakgu, Seoul 151-921, South Korea.
Journal of Biotechnology (Impact Factor: 2.88). 07/2008; 135(2):210-6. DOI: 10.1016/j.jbiotec.2008.01.021
Source: PubMed

ABSTRACT In this study, we demonstrated that the CSKSSDYQC-peptide ligand which was identified from a random phage-peptide library through an in vivo phage display technique with rats could prominently improve the transport efficiency of macromolecules, such as large filamentous phage particles (M13 bacteriophage), across the intestinal mucosal barrier. Synthetic CSKSSDYQC-peptide ligands significantly inhibited the binding of phage P1 encoding CSKSSDYQC-peptide ligands to the intestinal mucosal tissue and immunohistochemical analysis showed that the CSKSSDYQC-peptide ligands could be transported across the intestinal mucosal barrier via goblet cells as their specific gateway. Thus, we inferred that CSKSSDYQC-peptide ligand might have a specific receptor on the goblet cells and transported from intestinal lumen to systemic circulation by transcytosis mechanism. These results suggest that CSKSSDYQC-ligand could be a promising tool for development of an efficient oral delivery system for macromolecular therapeutics in the carrier-drug conjugate strategy.

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    • "In addition, TDA1 phage revealed competitive binding characteristic to rat visceral adipocytes against the synthetic TDA1 peptide ligands (Figure 2D). If binding affinity of the TDA1-encoding phage to adipocytes was due to a specific recognition between the peptide sequence of TDA1 and certain counterpart on the adipocytes, treatment of the synthetic TDA1 ligand could interfere binding of TDA1 phage to the target cells mutual competition (Arap et al., 1998; Kang et al., 2008; Wan et al., 2009). Thus, the result indicates an indirect evidence that there could be a specific receptor or recognition site for TDA1 on the adipocytes. "
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