Inductive effects in amino acids and peptides: Ionization constants and tryptophan fluorescence

Abstract

Although inductive effects in organic compounds are known to influence chemical properties such as ionization constants, their specific contribution to the properties/behavior of amino acids and functional groups in peptides remains largely unexplored. In this study we developed a computationally economical algorithm for ab initio calculation of the magnitude of inductive effects for non-aromatic molecules. The value obtained by the algorithm is called the Inductive Index and we observed a high correlation (R2 = 0.9427) between our calculations and the pKa values of the alpha-amino groups of amino acids with non-aromatic side-chains. Using a series of modified amino acids, we also found similarly high correlations (R2 > 0.9600) between Inductive Indexes and two wholly independent chemical properties: i) the pKa values of ionizable side-chains and, ii) the fluorescence response of the indole group of tryptophan. After assessing the applicability of the method of calculation at the amino acid level, we extended our study to tryptophan-containing peptides and established that inductive contributions of neighboring side-chains are transmitted through peptide bonds. We discuss possible contributions to the study of proteins.

Keywords

• Inductive effects
• Amino acids
• Peptides
• Ionization constants
• Tryptophan fluorescence
• Computational model