TY - JOUR
T1 - Chemically Optimized Antimyosin Fab Conjugates with Chelating Polymers
T2 - Importance of the Nature of the Protein-Polymer Single Site Covalent Bond for Biodistribution and Infarction Localization
AU - Trubetskoy, Vladimir S.
AU - Torchilin, Vladimir P.
AU - Narula, Jagat
AU - Khaw, Bann
PY - 1993/7/1
Y1 - 1993/7/1
N2 - Murine antimyosin Fab fragment was conjugated with in In-laheled N-terminal-modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo.
AB - Murine antimyosin Fab fragment was conjugated with in In-laheled N-terminal-modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0027630815&partnerID=8YFLogxK
U2 - 10.1021/bc00022a001
DO - 10.1021/bc00022a001
M3 - Article
C2 - 8218480
AN - SCOPUS:0027630815
SN - 1043-1802
VL - 4
SP - 251
EP - 255
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 4
ER -