TY - JOUR
T1 - Functional and Pharmacokinetic Properties of Antibody-Avidin Fusion Proteins
AU - Shin, Seung Uon
AU - Wu, Dafang
AU - Ramanathan, Rajeev
AU - Pardridge, William M.
AU - Morrison, Sherie L.
PY - 1997/5/15
Y1 - 1997/5/15
N2 - In an attempt to produce broadly useful targeting agents, genetic engineering and expression techniques have been used to produce Ab-avidin fusion proteins. Chicken avidin has been fused to mouse-human chimeric IgG3 at the end of CH1 (CH1-Av), immediately after the hinge (H-Av), and at the end of CH3 (CH3-Av). Fusion heavy chains of the expected molecular mass were expressed, assembled with a co-expressed light chain, and secreted. The resulting molecules continued to bind Ag. They also bound biotinylated human serum albumin; CH3-Av had reduced affinity (KA = 5.13 × 109 M-1) compared with the tetrameric avidin (KA = 1 × 1015 M-1), but greater affinity than monomeric avidin (KA = 1 × 107 M-1). Importantly, the avidin-IgG fusion proteins had a longer serum t1/2 in rats than avidin. The favorable pharmacokinetic parameters suggest that these avidin fusion proteins can be used effectively to deliver biotinylated ligands such as drugs and peptides to locales expressing any Ag recognized by the associated Ab.
AB - In an attempt to produce broadly useful targeting agents, genetic engineering and expression techniques have been used to produce Ab-avidin fusion proteins. Chicken avidin has been fused to mouse-human chimeric IgG3 at the end of CH1 (CH1-Av), immediately after the hinge (H-Av), and at the end of CH3 (CH3-Av). Fusion heavy chains of the expected molecular mass were expressed, assembled with a co-expressed light chain, and secreted. The resulting molecules continued to bind Ag. They also bound biotinylated human serum albumin; CH3-Av had reduced affinity (KA = 5.13 × 109 M-1) compared with the tetrameric avidin (KA = 1 × 1015 M-1), but greater affinity than monomeric avidin (KA = 1 × 107 M-1). Importantly, the avidin-IgG fusion proteins had a longer serum t1/2 in rats than avidin. The favorable pharmacokinetic parameters suggest that these avidin fusion proteins can be used effectively to deliver biotinylated ligands such as drugs and peptides to locales expressing any Ag recognized by the associated Ab.
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M3 - Article
C2 - 9144494
AN - SCOPUS:0031570025
VL - 158
SP - 4797
EP - 4804
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -