title: Application of N-C- or C-N-directed sequential native chemical ligation to the preparation of CXCL14 analogs and their biological evaluation.
abstract: CXCL14 is a chemokine that exhibits chemoattractant activity for activated macrophages, immature dendric cells, natural killer cells, and epithelial tumor cells. Its potential role as a metabolic regulator has recently been disclosed. However, a complete understanding of its physiological roles remains elusive. This is partly due to the lack of appropriate CXCL14-based molecular probes to explore the biological functions of CXCL14. In this context, we have developed synthetic protocols that provide access to a wide variety of CXCL14 analogs. Two sequential native chemical ligation (NCL) protocols, which proceed in opposite directions, have been used to assemble CXCL14 analogs from peptide fragments. The first involved a conventional C-N-directed sequential NCL, and afforded wild-type CXCL14. The other used peptide thioacids in N-C-directed elongation, and yielded CXCL14 analogs with molecular diversity at the C-terminal fragment. The CXCL14 analogs prepared showed biological activity on human monocytic leukemia-derived THP-1 cells that was comparable to that of wild-type CXCL14.
authors.affiliation: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, Shomachi, Tokushima, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tsuji
authors.forename: Akira
authors.initials: A
authors.lastname: Shigenaga
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Sumikawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanegashima
authors.forename: Kohei
authors.initials: K
authors.lastname: Sato
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aihara
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
mesh_terms: D000595:Amino Acid Sequence; D002244:Carbon / Q000737:chemistry; D045744:Cell Line, Tumor; D019743:Chemokines, CXC / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D010455:Peptides; D002244:Carbon; D009584:Nitrogen