title: Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors.
abstract: We recently reported that CXCL14 binds to CXCR4 with high affinity and inhibits CXCL12-mediated chemotaxis. Here we found that the C-terminal 51-77 amino acid residues of CXCL14 are responsible for CXCR4 binding. A disulfide dimer peptide of CXCL14(51-77) bound to CXCR4 with comparable affinity to full length CXCL14, and exhibited CXCL12 inhibitor activity. CXCR4 was efficiently internalized upon binding of dimeric CXCL14(51-77), thereby being reduced on the cell surface. Substitution of 5 amino acid residues in combination with the use of an oxime linker for dimerization increased the solubility and chemical stability of the dimeric CXCL14(51-77).
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanegashima
authors.forename: Kohei
authors.initials: K
authors.lastname: Tsuji
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Shigenaga
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: C515255:CXCL12 protein, human; C118056:CXCL14 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004220:Disulfides; D010455:Peptides
keywords: CD; CXCL12; CXCL14; CXCR4; FACS; TFA; circular dichroism; fluorescent activated cell sorting; trifluoroacetic acid; α-Helix