title: Functional and pharmacokinetic properties of antibody-avidin fusion proteins.
abstract: 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 C(H)1 (C(H)1-Av), immediately after the hinge (H-Av), and at the end of C(H)3 (C(H)3-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; C(H)3-Av had reduced affinity (K(A) = 5.13 x 10(9) M(-1)) compared with the tetrameric avidin (K(A) = 1 x 10(15) M(-1)), but greater affinity than monomeric avidin (K(A) = 1 x 10(7) 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.
authors.affiliation: Institute of Environment and Life Science, The Hallym Academy of Sciences, Hallym University, Kangwon-do, Korea.
authors.forename: S U
authors.initials: SU
authors.lastname: Shin
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Ramanathan
authors.forename: W M
authors.initials: WM
authors.lastname: Pardridge
authors.forename: S L
authors.initials: SL
authors.lastname: Morrison
mesh_terms: D000818:Animals; D001360:Avidin / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D001666:Binding Sites, Antibody; D001710:Biotin / Q000378:metabolism; D002645:Chickens; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship
chemical_list: D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D001360:Avidin; D001710:Biotin