Role of tyrosine and tryptophan in chemically modified serum albumin on its tissue distribution.
To investigate the effect of functional groups in bovine serum albumin (BSA) on its tissue distribution characteristics, tyrosine (Tyr) or tryptophan (Trp) residues of BSA were chemically modified by tetranitromethane (TNM) and 2-hydroxy-5-nitrobenzyl bromide (HNB), respectively. BSA was successfully modified with each reagent depending on the amount of the reagent added to the reaction mixture, and TNM- and HNB-modified BSA derivatives with different degrees of modification were obtained. Circular dichroism measurements showed that slight secondary and large tertiary changes were detectable as the degree of modification increased. After intravenous injection into mice, all synthetic BSA derivatives were eliminated very slowly from the systemic circulation. However, (111)In-TNM(6.6)- and (111)In-HNB(2.0)-BSA, derivatives with a high degree of modification, showed a slightly faster disappearance from the systemic circulation and slightly higher accumulation in the liver than (111)In-unmodified BSA. Pharmacokinetic analyses also demonstrated that the modification of Tyr or Trp residues on BSA had only marginal effects on tissue distribution. These results indicate that the Tyr and Trp residues have little effect on the tissue distribution characteristics of serum albumins, and that the specific modification of these residues may be a promising approach to designing sustained drug delivery systems using serum albumins.
Ma
Shen-Feng
SF
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Nishikawa
Makiya
M
Yabe
Yoshiyuki
Y
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D015077:2-Hydroxy-5-nitrobenzyl Bromide; D000818:Animals; D016503:Drug Delivery Systems; D007205:Indium Radioisotopes; D008297:Male; D051379:Mice; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013774:Tetranitromethane; D014018:Tissue Distribution; D014364:Tryptophan; D014443:Tyrosine
D007205:Indium Radioisotopes; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D015077:2-Hydroxy-5-nitrobenzyl Bromide; D014364:Tryptophan; D013774:Tetranitromethane