Octanol-water partition of nonzwitterionic peptides: Predictive power of a molecular size-based model

Peter Buchwald, Nicholas Bodor

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

A remarkably simple, molecular size-based model developed to predict octanol-water partition coefficients for organic compounds is tested on a set of 188 neutral peptides with available experimental partition data. Despite using only two parameters, it gives a promising correlation (r2 = 0.914; σ = 0.455, F = 1978.0), and predictions are in a realistic range even for larger peptides (cyclosporin, melanotan, sandostatin) where common, overparametrized fragment methods become quite unreliable. Ion-pair partitioning and the extraction constant formalism is briefly reviewed to describe the sigmoidal lipophilicity profile of ionizable, nonzwitterionic peptides. It seems possible to extend the present model to estimate apparent partition coefficients measured around neutral pH and physiological conditions for monoionic peptides; however, as no standard conditions are yet defined and only relatively small number of experimental data are available, the situation here is more complex.

Original languageEnglish (US)
Pages (from-to)86-99
Number of pages14
JournalProteins: Structure, Function and Genetics
Volume30
Issue number1
DOIs
StatePublished - Jan 1 1998

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Keywords

  • Cyclosporin
  • Gramicidin
  • Hydrogen bonding
  • Ion-pair partitioning
  • Lipophilicity profile
  • Molecular volume
  • Octreotide (sandostatin)
  • Partition coefficient

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

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