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.