Abstract:
:Site I of human serum albumin is an important and complex region for high-affinity binding of drugs. Equilibrium dialysis showed independent binding of dansyl-L-asparagine (DNSA) and n-alkyl p-aminobenzoates (p-ABEs) to regions Ib and Ic, respectively, in the pH range 6.0-9.0. However, individual binding of DNSA increased with pH in the same range. Binding of the four n-alkyl p-ABEs strongly perturbed the circular dichroism spectrum of bound DNSA, and the effect increased with concentration and the number of carbon atoms in the alkyl moiety. A similar effect was observed by increasing pH from 6.0 to 9.0, a pH range in which human serum albumin is known to undergo the neutral-to-base transition. The spectral changes propose spatial orientation changes of DNSA at region Ib. This proposal was supported by increased fluorescence anisotropy values: n-alkyl p-ABEs binding and the pH-dependent conformational change each restricted the mobility of the naphthalene ring of bound DNSA. Despite the similar effects on the spatial orientation of DNSA, clear differences were observed between the effects of n-alkyl p-ABEs and neutral-to-base transition. The former hardly changed the affinity and maximum fluorescence emission wavelength of bound DNSA; in contrast, the latter significantly affected them. The results give new information about site I and, according to our knowledge, represent a new type of ligand interaction, because the binding site of DNSA could be changed by simultaneous binding of the n-alkyl p-ABEs without affecting the binding constant.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Yamasaki K,Maruyama T,Takadate A,Suenaga A,Kragh-Hansen U,Otagiri Mdoi
10.1002/jps.20203subject
Has Abstractpub_date
2004-12-01 00:00:00pages
3004-12issue
12eissn
0022-3549issn
1520-6017pii
S0022-3549(16)39306-6journal_volume
93pub_type
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