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 alpha/beta-tetrapeptides (1-34) have been prepared employing solid-phase and in-parallel synthetic protocols. alpha/beta-Tetrapeptides 1-34 were prepared by a combination of three a-amino acid residues (alanine (Ala), phenylalanine (Phe), and isoleucine (Ille)) with one beta-amino acid residue (beta(3)-homophenylglycine). The corresponding complexes of several selected alpha/beta-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 beta-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 alpha/beta-tetrapeptide 12, HO2C-alpha-Phe-alpha-Phe-alpha-Ile-beta(3) -hPhg-NH2, as well as the conformational changes induced by the metal upon [tP + M+] complex formation. Copyright (C) 2008 John Wiley & Sons, Ltd.