Use of the harmonic mean to the determination of dissociation constants of stereoisomeric mixtures of biologically active compounds.
J Enzyme Inhib Med Chem
; 29(6): 884-94, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-24517366
Herein we introduce the derivation of a mathematical expression to evaluate the dissociation constant of a mixture of stereoisomers in equal amounts (KdMIX), when the corresponding dissociation constants (Kd) or medium response (MR50) of the pure stereoisomers are known; the final equation takes the form of the harmonic mean. In order to validate the equation, we carried out a bibliographic search of experimental data of enantiomeric molecules with biological activity, considering the Kd's or MR50's of the isolated enantiomers as well as that of the racemate. The comparisons between the experimental dissociation constants of the mixtures (KdEXP or MR50EXP) and the calculated values (KdMIX or MR50MIX) were consistent; the similarity between these values is supported through statistical analyses of group comparison and simple linear correlation. The equation we obtained, which corresponds to the harmonic mean, was used to predict the values of KdMIX (or MR50MIX) or Kd (or MR50) in systems when only two of the experimental values are known: either the dissociation constants of both enantiomers or the Kd (or MR50) of one of the enantiomers and dissociation constant of the racemate.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Modelos Estatísticos
/
Receptores de Superfície Celular
/
Células Eucarióticas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Reino Unido