PMID- 15614815
OWN - NLM
STAT- MEDLINE
DCOM- 20050608
LR  - 20131121
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 94
IP  - 2
DP  - 2005 Feb
TI  - Screening of bitterness-suppressing agents for quinine: the use of molecularly 
      imprinted polymers.
PG  - 353-62
AB  - The purpose of the present study was to examine the possibility of using 
      molecularly imprinted polymers (MIPs) to screen for bitterness-suppressing 
      agents. Quinine was selected as the bitter substance standard. L-arginine 
      (L-Arg), L-ornithine (L-Orn), L-lysine (L-Lys), and L-citrulline (L-Ctr) were 
      tested as bitterness suppressant candidates. In a high-performance liquid 
      chromatography study using a uniformly sized MIP for cinchonidine, which has a 
      very similar structure to quinine, the retention factor (k) of quinine was 
      significantly shortened by the addition of L-Arg or L-Orn to the mobile phase, 
      whereas slight or no decrease was observed when L-Ctr and L-Lys were added. The 
      abilities of these amino acids to decrease the k of quinine were ranked in the 
      following order: L-Arg = (L-Orn >(L-Ctr >>(L-Lys. A linear relationship between 
      the reciprocal of k and the concentration of the amino acids indicated a single 
      competitive model at a single site. The magnitude of the association constants 
      obtained seemed to be directly related to the inhibitory effect of the test 
      substances on the affinity of quinine for the receptor site. Nuclear magnetic 
      resonance and molecular modeling studies suggested a one-to-two 
      hydrogen-bonding-based complex formation of one quinine molecule with two 
      methacrylic acid molecules (Q-2MAA) in chloroform. In the molecular modeling 
      studies, the N--N distance of the quinine molecule in the assumed Q-2MAA complex 
      was calculated to be 5.12 angstroms, similar to the N - N distances of the two 
      amino acid complexes (L-Arg-2MAA, L-Orn-2MAA), which were 4.84 and 5.30 
      angstroms, respectively. This suggests that L-Arg and L-Orn may compete with the 
      quinine molecule in the cinchonidine-imprinted space. Finally, the results of 
      human gustatory sensation tests correlated well with the MIP data. The proposed 
      method using MIPs seems to have a potential for screening bitterness-suppressing 
      agents for quinine.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Ogawa, Tazuko
AU  - Ogawa T
AD  - School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien 
      9-Bancho, Nishinomiya City 663-8179, Japan. mwu29310@mwu.mukogawa-u.ac.jp
FAU - Hoshina, Kaori
AU  - Hoshina K
FAU - Haginaka, Jun
AU  - Haginaka J
FAU - Honda, Chie
AU  - Honda C
FAU - Tanimoto, Toshiko
AU  - Tanimoto T
FAU - Uchida, Takahiro
AU  - Uchida T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Sweetening Agents)
RN  - 29VT07BGDA (Citrulline)
RN  - 94ZLA3W45F (Arginine)
RN  - A7V27PHC7A (Quinine)
RN  - E524N2IXA3 (Ornithine)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Arginine/chemistry/pharmacology
MH  - Chromatography, High Pressure Liquid
MH  - Citrulline/chemistry/pharmacology
MH  - Drug Evaluation, Preclinical
MH  - Drug Interactions
MH  - Humans
MH  - Lysine/chemistry/pharmacology
MH  - Models, Biological
MH  - Models, Molecular
MH  - Ornithine/chemistry/pharmacology
MH  - Quinine/chemistry/*pharmacology
MH  - Reference Standards
MH  - Sweetening Agents/chemistry/pharmacology
MH  - Taste/*drug effects
MH  - Taste Threshold/drug effects
EDAT- 2004/12/23 09:00
MHDA- 2005/06/09 09:00
CRDT- 2004/12/23 09:00
PHST- 2004/12/23 09:00 [pubmed]
PHST- 2005/06/09 09:00 [medline]
PHST- 2004/12/23 09:00 [entrez]
AID - S0022-3549(16)31705-1 [pii]
AID - 10.1002/jps.20248 [doi]
PST - ppublish
SO  - J Pharm Sci. 2005 Feb;94(2):353-62. doi: 10.1002/jps.20248.