FC 131

Rapid detection of the Fc gamma RIIA-H/R 131 ligand-binding polymorphism using an allele-specific restriction enzyme digestion (ASRED).[Pubmed:8960098]

J Immunol Methods. 1996 Nov 29;199(1):55-9.

A polymorphism of the gene for Fc gamma RIIA, arginine (R) or histidine (H) at position 131, alters the ability of the receptor to bind certain IgG subclasses. Identification of the Fc gamma RIIA-H/R 131 genotype has assumed increasing importance in disorders of host defense, immunohematologic diseases and systemic autoimmune disorders. We report a new method for determination of this genotype in which an allele-specific restriction enzyme site is introduced into an Fc gamma RIIA PCR product from genomic DNA, and polymorphism assignment is determined by restriction enzyme digestion followed by agarose gel electrophoresis. This method is more rapid, more reliable and less expensive than currently available methods.

Fc gamma RIIA H/R 131 polymorphism, subclass-specific IgG anti-heparin/platelet factor 4 antibodies and clinical course in patients with heparin-induced thrombocytopenia and thrombosis.[Pubmed:9002937]

Blood. 1997 Jan 15;89(2):370-5.

The explanation why only a subset of patients with heparin-induced thrombocytopenia (HIT) develop clinically apparent thromboses (HITT) remains uncertain. It has been proposed that platelet activation induced by cross-linking of Fc gamma RIIA by anti-heparin/platelet factor 4 (PF4) antibodies is central to the pathogenesis of thrombosis. The observation that a common functional polymorphism of Fc gamma RIIA, involving either an arginine (R) or histidine (H) at amino acid 131, may underlie disease susceptibility prompted us to investigate the prevalence of receptor isoforms in patients with HIT and HITT. Furthermore, because these isoforms reportedly differ in their avidity for immune complexes containing human IgG2, we also analyzed sera from patients with HIT and HITT for the prevalence of various subclass-specific IgG anti-heparin/PF4 antibodies. No difference in the allele frequency of Fc gamma RIIA-H131 or R131 was identified among 13 patients with HIT or 23 with HITT compared with 102 controls (chi 2 = 1.21, P = .8). Furthermore, although most patients had IgG2 antibodies (62%), IgG, was the predominant subclass in 30 of the 34 patients with IgG anti-heparin/PF4 antibodies and in 12 was the exclusive subclass found. Also, there was no association between the concordance of IgG2 anti-heparin/ PF4 antibodies and the expression of Fc gamma RIIA-H131 in patients with HITT compared with patients with thrombocytopenia alone. These results make it unlikely that the Fc gamma RIIA-H131 isoform or IgG2 anti-heparin/PF4 antibodies are required to develop HITT, suggesting that factors in addition to cross-linking of Fc gamma RIIA receptors contribute to the pathogenesis of thrombosis in patients with heparin-dependent antiplatelet: antibodies.

Stereoselective synthesis of [L-Arg-L/D-3-(2-naphthyl)alanine]-type (E)-alkene dipeptide isosteres and its application to the synthesis and biological evaluation of pseudopeptide analogues of the CXCR4 antagonist FC131.[Pubmed:15658852]

J Med Chem. 2005 Jan 27;48(2):380-91.

L,L-Type and L,D-type (E)-alkene dipeptide isosteres (EADIs) that have unnatural side chains at the alpha-position were synthesized by the combination of stereoselective aziridinyl ring-opening reactions and organozinc-copper-mediated anti-S(N)2' reactions toward a single substrate of gamma,delta-cis-gamma,delta-epimino (E)-alpha,beta-enoate. The utility of this methodology was demonstrated by the stereoselective synthesis of a set of diastereomeric EADIs of L-Arg-L/D-3-(2-naphthyl)alanine (Nal) that is contained in a small CXCR4 antagonist FC131 [cyclo(-D-Tyr-Arg-Arg-Nal-Gly-)]. Furthermore, a (Nal-Gly)-type EADI was synthesized by samarium diiodide (SmI(2))-induced reduction of a gamma-acetoxy-alpha,beta-enoate. Several FC131 analogues, in which these EADIs were inserted for reduction of their peptide character, were synthesized with analogues containing reduced amide-type dipeptide isosteres to investigate the importance of these amide bonds for anti-HIV and CXCR4-antagonistic activity.