title: Modulation of the stacking interaction of MN4 (M=Pt, Pd, Au) complexes with tryptophan through N-heterocyclic ligands.
abstract: A survey of selected N-heterocycle ligands showed that platination of 4-N-dimethylaminopyridine (DMAP) in [Pt(dien)L](2+) (dien=diethylenetriamine) gave especially strong π-π stacking interactions with tryptophan and the tryptophan-containing C-terminal zinc finger (ZF) of the HIV (human immunodeficiency virus) nucleocapsid protein NCp7. The association constants (all at 10(3)M(-1)) were significantly stronger (25.0 and 28.1 for tryptophan and ZF respectively) than those previously measured for the purine nucleobase 9-ethylguanine (9EtG) in [Pt(dien)(9EtG)](2+) (6.88 and 7.55 for tryptophan and ZF respectively). Extension to Pd and Au complexes also confirmed the utility of DMAP in assisting stacking interactions. The results confirm the utility of a "bioinorganic" approach to targeting and inactivation of medicinal chemistry targets using the dual approach of target recognition (non-covalent) followed by target fixation (covalent).
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA.
authors.forename: Samantha D
authors.initials: SD
authors.lastname: Tsotsoros
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Bate
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA.
authors.forename: Martina G
authors.initials: MG
authors.lastname: Dows
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Spell
authors.affiliation: Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA 23529, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bayse
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA. Electronic address: npfarrell@vcu.edu.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Farrell
mesh_terms: D000595:Amino Acid Sequence; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006678:HIV / Q000737:chemistry / Q000235:genetics; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry*; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D056831:Coordination Complexes; D006571:Heterocyclic Compounds; D008024:Ligands; D010984:Platinum; D010165:Palladium; D006046:Gold; D014364:Tryptophan
keywords: HIV NCp7 peptide; Platinum–metal heterocycle ligands; Tryptophan stacking