SYN1327 is a potent monomeric cyclic competitive antagonistic peptide targeting the neonatal Fc receptor ( FcRn ), with a K d of 31 nM for human FcRn at pH 6 and a K d of 170 nM at pH 7.4. SYN1327 competitively binds to the IgG-binding site of FcRn and inhibits the binding of human IgG to FcRn. SYN1327 acts as the monomeric precursor of the dimeric peptide SYN1436. SYN1327 can be used in studies related to IgG-mediated autoimmune diseases [1] [2] [3].
In Vivo, SYN1327 (10 mg/kg; i.v.; daily; 4 days) does not reduce serum human IgG levels in human FcRn transgenic mice[2].
In Vitro, SYN1327 exhibits pH-dependent binding to FcRn, with a binding constant of 31 nM at pH 6.0 and 170 nM at pH 7.4[1][2][3]. SYN1327 inhibits the interaction between hIgG and immobilized shFcRn in ELISA-based assays at pH 6 with an IC50 of 570 nM; in FACS-based competition assays, it inhibits the binding of fluorescently labeled hIgG to 293c11 cells expressing hFcRn at pH 6, with an IC50 of 510 nM[2]. SYN1327 potently binds to human and cynomolgus monkey FcRn at pH 6, but its binding affinity for mouse and rat FcRn is approximately 1000-fold weaker, and it only exhibits weak non-specific binding to human HLA-A2[2]. SYN1327 inhibits the interaction between human IgG and human FcRn in in vitro ELISA assays, with an IC50 of 520 nM[3].
References:
[1]. Song X N, et al. The effect of pH and ligand density on the endocytosis and exocytosis process of FcBP decorated PEG‑PCL micelles on Caco‑2 cells[J]. Acta Pharmaceutica Sinica, 2017, 52(8): 1331‑1336.
[2]. Mezo AR, et al. Reduction of IgG in nonhuman primates by a peptide antagonist of the neonatal Fc receptor FcRn. Proceedings of the National Academy of Sciences of the United States of America. 2008 Feb 19;105(7):2337-42.
[3]. McDonnell KA, et al. Synthesis and structure-activity relationships of dimeric peptide antagonists of the human immunoglobulin G-human neonatal Fc receptor (IgG-FcRn) interaction. Journal of medicinal chemistry. 2010 Feb 25;53(4):1587-96.
In Vivo, SYN1327 (10 mg/kg; i.v.; daily; 4 days) does not reduce serum human IgG levels in human FcRn transgenic mice[2].
In Vitro, SYN1327 exhibits pH-dependent binding to FcRn, with a binding constant of 31 nM at pH 6.0 and 170 nM at pH 7.4[1][2][3]. SYN1327 inhibits the interaction between hIgG and immobilized shFcRn in ELISA-based assays at pH 6 with an IC50 of 570 nM; in FACS-based competition assays, it inhibits the binding of fluorescently labeled hIgG to 293c11 cells expressing hFcRn at pH 6, with an IC50 of 510 nM[2]. SYN1327 potently binds to human and cynomolgus monkey FcRn at pH 6, but its binding affinity for mouse and rat FcRn is approximately 1000-fold weaker, and it only exhibits weak non-specific binding to human HLA-A2[2]. SYN1327 inhibits the interaction between human IgG and human FcRn in in vitro ELISA assays, with an IC50 of 520 nM[3].
References:
[1]. Song X N, et al. The effect of pH and ligand density on the endocytosis and exocytosis process of FcBP decorated PEG‑PCL micelles on Caco‑2 cells[J]. Acta Pharmaceutica Sinica, 2017, 52(8): 1331‑1336.
[2]. Mezo AR, et al. Reduction of IgG in nonhuman primates by a peptide antagonist of the neonatal Fc receptor FcRn. Proceedings of the National Academy of Sciences of the United States of America. 2008 Feb 19;105(7):2337-42.
[3]. McDonnell KA, et al. Synthesis and structure-activity relationships of dimeric peptide antagonists of the human immunoglobulin G-human neonatal Fc receptor (IgG-FcRn) interaction. Journal of medicinal chemistry. 2010 Feb 25;53(4):1587-96.