Solid phase synthesis of novel α / β ‐tetrapeptides, electrospray ionization mass spectrometric evaluation of their metal cation complexation behavior, and conformational analysis using density functional theory (DFT)

Thirty‐four novel α / β ‐tetrapeptides ( 1–34 ) have been prepared employing solid‐phase and in‐parallel synthetic protocols. α / β ‐Tetrapeptides 1 – 34 were prepared by a combination of three α ‐amino acid residues (alanine (Ala), phenylalanine (Phe), and isoleucine (Ile)) with one β ‐amino acid residue ( β 3 ‐homophenylglycine). The corresponding complexes of several selected α / β ‐tetrapeptides with alkali, alkaline earth, and transition metals, [tP + M + ], were evaluated using ion electrospray‐ionization mass spectrometry (ESI‐MS). According to the results from analysis of mixtures, we can conclude that the position of the β ‐amino acid is determinant in the affinity toward different metal cations. Computational modeling (DFT, B3LYP 6‐311++G) provided useful information regarding the most likely coordination sites of the metal ions on the receptor α / β ‐tetrapeptide 12 , HO 2 C‐ α ‐Phe‐ α ‐Phe‐ α ‐Ile‐ β 3 ‐hPhg‐NH 2 , as well as the conformational changes induced by the metal upon [tP + M + ] complex formation. Copyright © 2008 John Wiley & Sons, Ltd.