Conformation and mobility of tyrosine side chain in tetrapeptides: Specific effects of cis‐ and trans ‐proline in Tyr‐Pro‐ and Pro‐Tyr‐segments

Abstract

We examined the properties of tyrosine in four free tetrapeptides: Ala-Ala-Tyr-Ala (AATA), Ala-Pro-Tyr-Ala (APTA), Ala-Tyr-Ala-Ala (ATAA) and Ala-Tyr-Pro-Ala (ATPA) by CD, n.m.r. and energy calculations. Experimental data (the aromatic ¹L_b signal, rotamer populations around the C_α-C_β bond (x¹), rotations around C_β- C_γ(χ²), chemical shifts of ortho- and meta-protons in the phenolic ring (in aqueous and Me₂SO solutions), NH proton temperature coefficients and vicinal coupling constants ³J_NH-CαH in the backbone (Me₂SO solution) were compared with calculated minimum energy conformations. We find qualitative agreement between the results of the different techniques with respect to global tendencies of conformational behaviour: we present experimental evidence showing that the presence of proline in the sequence has a more pronounced effect on the side chain organization of the residues preceding it than on one succeeding it. This steric influence of proline on its immediate neighbor is even stronger in the cis isomer than in the more common trans isomer. The strong preference for Rotamer II (χ¹ = 180°) over Rotamer I (χ¹ = - 60°) in ATPA (cis -form) concomitant with a noticeable deviation of χ² is a striking example.