title: Configurations of nickel-cyclam antiviral complexes and protein recognition.
abstract: Nickel(II)-xylylbicyclam is a potent anti-HIV agent and binds strongly to the CXCR4 co-receptor. We have investigated configurational equilibria of Ni(II)-cyclam derivatives, since these are important for receptor recognition. Crystallographic studies show that both trans and cis configurations are readily formed: [Ni(cyclam)(OAc)(2)] x H(2)O adopts the trans-III configuration with axial monodentate acetates, as does [Ni(benzylcyclam)(NO(3))(2)] with axial nitrate ligands, whereas [Ni(benzylcyclam)(OAc)](OAc)2 x H(2)O has an unusual folded cis-V configuration with Ni(II) coordination to bidentate acetate. UV/Vis and NMR studies show that the octahedral trans-III configuration slowly converts to square-planar trans-I in aqueous solution. For Ni(II)-xylylbicyclam, a mixture of cis-V and trans-I configurations was detected in solution. X-ray diffraction studies showed that crystals of lysozyme soaked in Ni(II)-cyclam or Ni(II) (2)-xylylbicyclam contain two major binding sites, one involving Ni(II) coordination to Asp101 and hydrophobic interactions between the cyclam ring and Trp62 and Trp63, and the second hydrophobic interactions with Trp123. For Ni(II)-cyclam bound to Asp101, the cis-V configuration predominates.
authors.affiliation: School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Hunter
authors.forename: Iain W
authors.initials: IW
authors.lastname: McNae
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Simpson
authors.forename: Alison M
authors.initials: AM
authors.lastname: Smith
authors.forename: Stephen
authors.initials: S
authors.lastname: Moggach
authors.forename: Fraser
authors.initials: F
authors.lastname: White
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Walkinshaw
authors.forename: Simon
authors.initials: S
authors.lastname: Parsons
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry; D009532:Nickel / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D006571:Heterocyclic Compounds; C024560:cyclam; D009532:Nickel; D009113:Muramidase