Handedness control of peptide helices by amino acid side‐chain chirality: Ile/aIle peptides

Abstract

A set of four hexapeptide sequences, each characterized by four strongly helicogenic Aib residues and all combinations of two isomeric Ile/aIle residues at positions 2 and 5, was synthesized by solution methods and fully characterized. A detailed solution (by FT-IR absorption, NMR, and CD techniques) and solid/crystalline state (by X-ray diffraction) conformational investigation allowed us to validate our assumption that all four peptides are folded in well-developed 3(10)-helical structures. However, the most relevant conformational conclusion extracted from the present 3D-analysis is that the handedness of the 3(10)-helical structures formed does not seem to be sensitive to the configurational change at the beta-carbon atom of the constituent Ile versus the diastereomeric aIle residues (in other words, the dominant control on this important structural parameter appears to be exerted by the chirality of the amino acid alpha-carbon atom). These results complement published findings on the diverging relative stabilities of the intermolecularly H-bonded beta-sheet structures generated by Ile versus aIle homo-oligopeptides.

Experimental aspects of solid state circular dichroism

“…Pellet techniques have been used in many laboratories, for a variety of samples including biomolecules, [32][33][34][35][36][37][38][39][40][41][42][43] both in the UV-vis (ECD) and in the IR (VCD).…”

Handedness preference and switching of peptide helices. Part I: Helices based on protein amino acids

“…A few years ago, we made efforts to address the issue of handedness control of peptide helices via amino acid side‐chain chirality by investigating the conformational properties of terminally protected (or blocked), helical diastereomeric hexapeptides rich in Ile or a Ile (where a stands for allo ) residues (Figure ) .…”

Structure‐guided RP‐HPLC chromatography of diastereomeric α‐helical peptide analogs substituted with single amino acid stereoisomers

“…Therefore, four stereoisomers are possible. These isomers are: l ‐Ile [(2 S ,3 S )‐2‐amino‐3‐methyl‐valeric acid], l ‐ allo ‐Ile [(2 S ,3 R )‐2‐amino‐3‐methyl‐valeric acid], d ‐Ile [(2 R ,3 R )‐2‐amino‐3‐methyl‐valeric acid] and d ‐ allo ‐Ile [(2 R ,3 S )‐2‐amino‐3‐methyl‐valeric acid] (Andreetto et al ., ). The structures of the four Fmoc‐protected Ile configurational isomers used in this study are shown in Fig.…”

“…With the exception of glycine, the remaining 19 proteinogenic amino acids contain at least one chiral carbon atom, with isoleucine (Ile) and threonine also containing a second chiral carbon atom. Such chiral centers allow the existence of amino acid enantiomers (Andreetto et al, 2006;Ilisz et al, 2010). It is well known that L-and D-enantiomeric forms of amino acids substituted into peptides and proteins can have profoundly different effects on stability and biological activity (Chen et al, 2005;Kondejewski et al, 1999;Lee et al, 2004;Oren and Shai, 1997;Papo and Shai, 2005).…”