Tryptophan rich peptides: Influence of indole rings on backbone conformation

Abstract

Synthetic peptides with defined secondary structure scaffolds, namely hairpins and helices, containing tryptophan residues, have been investigated in this study to probe the influence of a large number of aromatic amino acids on backbone conformations. Solution NMR investigations of Boc-W-L-W-(D)P-G-W-L-W-OMe (peptide 1), designed to form a well-folded hairpin, clearly indicates the influence of flanking aromatic residues at the (D)Pro-Gly region on both turn nucleation and strand propagation. Indole-pyrrolidine interactions in this peptide lead to the formation of the less-frequent type I' turn at the (D)Pro-Gly segment and frayed strand regions, with the strand residues adopting local helical conformations. An analog of peptide 1 with an Aib-Gly turn-nucleated hairpin (Boc-W-L-W-U-G-W-L-W-OMe (peptide 2)) shows a preference for helical structures in solution, in both chloroform and methanol. Peptides with either one (Boc-W-L-W-U-W-L-W-OMe (peptide 3)) or two (Boc-U-W-L-W-U-W-L-W-OMe (peptide 4)) helix-nucleating Aib residues give rise to the well-folded helical conformations in the chloroform solution. The results are indicative of a preference for helical folding in peptides containing a large number of Trp residues. Investigation of a tetrapeptide analog of peptide 2, Boc-W-U-G-W-OMe (peptide 5), in solution and in the crystal state (by X-ray diffraction), also indicates a preference for a helical fold. Additionally, peptide 5 is stabilized in crystals by both aromatic interactions and an array of weak interactions. Examination of Trp-rich sequences in protein structures, however, reveals no secondary structure preference, suggesting that other stabilizing interactions in a well-folded protein may offset the influence of indole rings on backbone conformations.

Aromatische Ringe in chemischer und biologischer Erkennung: Energien und Strukturen

“…[149] Wasserstoffbrücken-Kontakte zwischen der N-H-Einheit von Amin-und Amidresten mit Seitenketten aromatischer Aminosäuren tragen signifikant zur Stabilität von Proteinen und zur Protein-Ligand-Bindung bei. [150] Die N-H···p-Wechselwirkungen zwischen Amiden und Seitenketten aromatischer Aminosäuren wurden mithilfe von Peptidmodellsystemen identifiziert und untersucht, [151] z. B. im Falle der Ligandenbindung an Chk1-Kinase, [152] in der der aromatische Ring des Inhibitors (K i = 26 nm) N-H···p-Wechselwirkungen mit der Amid-NH-Gruppe von Ser147/Asp148 eingeht (Abbildung 15).…”

Juxtamembrane tryptophans have distinct roles in defining the OmpX barrel–micelle boundary and facilitating protein–micelle association

“…The aromatic girdle in membrane proteins, preferentially localized at the membrane interface, is speculated to play an important role in directing interactions critical for membrane protein folding and anchoring [8][9][10][11][12][13][14][15][16]. Particularly, the indole presents unique properties of possessing the largest non-polar surface area, along with hydrogen bonding capability [15,17]. High polarizability makes tryptophan the ideal amphiphilic residue for stabilizing the membrane-protein interface [15].…”

Calculation of strong and weak interactions in TDA1 and RangDP52 by the kernel energy method

“…It has been noted that cooperativity among weak interactions allows them to contribute effectively to tighten molecular packing in crystals to an extent beyond that associated with ordinary van der Waals forces. This can affect the thermal and electronic properties of molecules, including electron mobility, and physical properties such as hardness, melting point, and crystal stability (1)(2)(3)(4). Because it is of increasing interest to recognize the significant and sometimes subtle effects on molecular properties caused by weak interactions, we have undertaken a quantum mechanical study of their energetics in crystals of 2 molecules that may stand as examples in addition to the compounds discussed by Desiraju In the molecules to be studied the crystal structures and atomic coordinates are known (2,3).…”