Identification of a peptide sequence that improves transport of macromolecules across the intestinal mucosal barrier targeting goblet cells.
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.
Kang
Sang Kee
SK
School of Agricultural Biotechnology, Seoul National University, San 56-1, Sillimdong, Gwanakgu, Seoul 151-921, South Korea.
Woo
Jung Hee
JH
Kim
Min Kook
MK
Woo
Sang Soo
SS
Choi
Jin Hyuk
JH
Lee
Hong Gu
HG
Lee
Nam Kyung
NK
Choi
Yun Jaie
YJ
D000595:Amino Acid Sequence; D000818:Animals; D017104:Bacteriophage M13 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017101:Bacteriophage P1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001692:Biological Transport; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism / Q000821:virology; D008297:Male; D008856:Microscopy, Fluorescence; D008962:Models, Theoretical; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D019151:Peptide Library; D010455:Peptides