title: Low-molecular-weight CXCR4 ligands with variable spacers.
abstract: Low-molecular-weight CXCR4 ligands based on known lead compounds including the 14-mer peptide T140, the cyclic pentapeptide FC131, peptide mimetics, and dipicolylamine-containing compounds were designed and synthesized. Three types of aromatic spacers, 1,4-phenylenedimethanamine, naphthalene-2,6-diyldimethanamine, and [1,1'-biphenyl]-4,4'-diyldimethanamine, were used to build four pharmacophore groups. As pharmacophore groups, 2-pyridylmethyl and 1-naphthylmethyl are present in all of the compounds, and several aromatic groups and a cationic group from 1-propylguanidine and 1,1,3,3-tetramethyl-2-propylguanidine were also used. Several compounds showed significant CXCR4 binding affinity, and zinc(II) complexation of bis(pyridin-2-ylmethyl)amine moieties resulted in a remarkable increase in CXCR4 binding affinity.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Narumi
authors.forename: Haruo
authors.initials: H
authors.lastname: Aikawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Chie
authors.initials: C
authors.lastname: Hashimoto
authors.forename: Nami
authors.initials: N
authors.lastname: Ohashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Nomura
authors.forename: Takuya
authors.initials: T
authors.lastname: Kobayakawa
authors.forename: Hikaru
authors.initials: H
authors.lastname: Takano
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Murakami
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
mesh_terms: D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology
chemical_list: D056831:Coordination Complexes; D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D057786:Peptidomimetics; D019718:Receptors, CXCR4; D054852:Small Molecule Libraries; C116977:T140 peptide; D015032:Zinc