Sequence specificity of the PHSRN peptide from fibronectin on corneal epithelial migration.
The Pro-His-Ser-Arg-Asn (PHSRN) sequence in fibronectin is a second cell-binding site that synergistically affects with Arg-Gly-Asp. The PHSRN peptide also induces cell invasion and accelerates wound healing. Here, we examined the sequence specificity of PHSRN on corneal epithelial migration using various synthetic peptides. Elongation and deletion analyses of Ac-PHSRN-NH(2) suggest that the five amino acid length was a minimum and essential sequence for promotion of rabbit corneal epithelial migration ex vivo. Additionally, alanine substituted analysis indicated that the Ser- and Arg-residues are critical for the biological activities. The Ser-Arg motif is involved in various biologically active peptides, suggesting that the unique sequence interacts with cellular receptor(s) and regulates biological functions. Further, the N-acetyl and C-amide of Ac-PHSRN-NH(2) contributed effectively for the chemical stability in tears. The Ac-PHSRN-NH(2) peptide has potential to use as a therapeutic reagent especially for corneal wound healing.
Hattori
Atsushi
A
Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Hozumi
Kentaro
K
Ko
Ji-Ae
JA
Chikama
Tai-ichiro
T
Oomikawa
Kayo
K
Kato
Junta
J
Ishida
Kazuumi
K
Hoshi
Norio
N
Katagiri
Fumihiko
F
Kikkawa
Yamato
Y
Nomizu
Motoyoshi
M
Nishida
Teruo
T
D000409:Alanine / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D003315:Cornea / Q000166:cytology / Q000187:drug effects*; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011817:Rabbits; D012694:Serine / Q000737:chemistry / Q000235:genetics
D005353:Fibronectins; D010446:Peptide Fragments; C495978:prolyl-histidyl-seryl-arginyl-asparagine; D012694:Serine; D000409:Alanine