title: Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES.
abstract: BACKGROUND
  RANTES is a CC-type chemokine protein that acts as a chemoattractant for several kinds of leukocytes, playing an important pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1) into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and inhibits HIV-1 entry into peripheral blood cells. Interaction with chemokine receptors involves a distinct set of residues at the amino terminus of RANTES. This finding was utilized in the development of a chemically modified aminooxypentane derivative of RANTES, AOP-RANTES, that was originally produced from the recombinant protein using semisynthetic methods.
  
  
  RESULTS
  AOP-RANTES has been produced by a novel total chemical synthesis that provides efficient, direct access to large amounts of this anti-HIV protein analog. The crystal structure of chemically synthesized AOP-RANTES has been solved and refined at 1.6 A resolution. The protein is a dimer, with the amino-terminal pentane oxime moiety clearly defined.
  
  
  CONCLUSIONS
  Total chemical synthesis of AOP-RANTES provides a convenient method of producing the multi-milligram quantities of this protein needed to investigate the molecular basis of receptor binding and antiviral activity. This work provides the first truly high-resolution structure of a RANTES protein, although the structure of RANTES was known from previous nuclear magnetic resonance (NMR) determinations.
authors.affiliation: Gryphon Sciences, 250 East Grand Avenue, Suite 90, South San Francisco,CA 94080, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wilken
authors.forename: D
authors.initials: D
authors.lastname: Hoover
authors.forename: D A
authors.initials: DA
authors.lastname: Thompson
authors.forename: P N
authors.initials: PN
authors.lastname: Barlow
authors.forename: H
authors.initials: H
authors.lastname: McSparron
authors.forename: L
authors.initials: L
authors.lastname: Picard
authors.forename: A
authors.initials: A
authors.lastname: Wlodawer
authors.forename: J
authors.initials: J
authors.lastname: Lubkowski
authors.forename: S B
authors.initials: SB
authors.lastname: Kent
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018946:Chemokine CCL5 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D019380:Anti-HIV Agents; D018946:Chemokine CCL5; D010455:Peptides; C111989:aminooxypentane-RANTES