The Ant‐Pro Reverse‐Turn Motif. Structural Features and Conformational Characteristics

Abstract

This article details the characteristic conformational features of the Ant‐Pro reverse turn ― a folded pseudo β‐turn motif that displays a closed nine‐membered‐ring hydrogen‐bonded network involving just two amino acid residues, namely anthranilic acid (Ant; a constrained β‐amino acid), and proline (Pro; a constrained α‐amino acid). The results from the extensive investigation of ten crystal structures and their NMR conformations in the solution state provide a clear idea about the conformational characteristics of the Ant‐Pro reverse turn. The Ant and Pro residues, which form the turn segment, maintain a perfect antiperiplanar orientation throughout, leaving little possibility for the formation of the otherwise possible six‐membered hydrogen‐bonding that requires a coplanar disposition of the two amino acid residues, as clearly evident from investigation of several crystal structures. The closed hydrogen‐bonded network observed in the Ant‐Pro reverse turn motif, formed in the forward direction of the sequence (1→2 amino acid interactions) involving only two amino acid residues, is in stark contrast to the native β‐turns that involve four residues to form hydrogen‐bonded network featuring backward 1←4 amino acid interactions. The readily available two‐residue Ant‐Pro motif raises the possibility of a practical utility, particularly in the application of rigidifying flexible peptide backbones by inserting the robust Ant‐Pro reverse turn motifs into their backbone.

Synthesis and Analysis of the Conformational Preferences of 5‐Aminomethyloxazolidine‐2,4‐dione Scaffolds: First Examples of β2‐ and β2, 2‐Homo‐Freidinger Lactam Analogues

“…[47] This structure requires only the mixed b/a-dipeptide to display the closed hydrogen-bonded network (Figure 7 a). To our knowledge, 10 a represents a very rare example of a short sequence showing this kind of pseudo b-turn, [48] although it was observed in linear oligomers composed of repetitive a/b-units (e.g., Figure 7 c, d). This structure is in contrast to native bturns (Figure 7 b), which involve four residues to form the hydrogen-bonded structure in the opposite direction (residues 17 !4).…”

“…This structure is in contrast to native bturns (Figure 7 b), which involve four residues to form the hydrogen-bonded structure in the opposite direction (residues 17 !4). To our knowledge, 10 a represents a very rare example of a short sequence showing this kind of pseudo b-turn, [48] although it was observed in linear oligomers composed of repetitive a/b-units (e.g., Figure 7 c, d).…”

“…[33f] In contrast, the peptide Boc-[(R)-Phe-(R)-b 3 -homo-Val] 2 -(R)-PheOMe (Figure 7 c), [46] 'heterochiral' because the b 3 -residues derived from l-a-residues, was shown to adopt a mixed structure characterized by one classic 11-membered i7 !i + 3 hydrogen bond, and a distinct ninemembered 27 !1 hydrogen-bond with opposite orientation. [48] Remarkably, the characteristic Freidinger-lactam-like structure of the mixed b 2 /a-dipeptide mimetic Amo-Phe induced 10 a to adopt, in a very competitive and biomimetic environment, a significant population of folded geometries, without the concomitant assistance of further constraint-inducers, and without the cooperative effect of repetitive units. The structure was explained as the result of the combined intrinsic conformational preferences of two local constraints and the repetitive a/b-hybrid structure.…”

“…Later studies confirmed the stability of the turn motifs featuring the nine-membered hydrogenbond ring also in tripeptides containing a distinct Ant-Pro scaffold. [48] Remarkably, the characteristic Freidinger-lactam-like structure of the mixed b 2 /a-dipeptide mimetic Amo-Phe induced 10 a to adopt, in a very competitive and biomimetic environment, a significant population of folded geometries, without the concomitant assistance of further constraint-inducers, and without the cooperative effect of repetitive units.…”

Crystal structure and Hirshfeld surface analysis of dichlorido(methanol-κO)bis(2-methylpyridine-κN)copper(II)

“…Both organic (from simple molecules to peptides and proteins) and inorganic complexes have been known for more than a century and are central to modern chemistry because of their fascinating, aesthetic architectures and multiple applications (Gan et al, 2011;Gellman, 1998;Thorat et al, 2013;Vijayadas et al, 2013;Ziach et al, 2018). Recently, coordination compounds have been reported that find applications in fields such as catalysis, gas storage, separation technology and molecular sensing (Mueller et al, 2006;Wan et al, 2006;Fé rey et al, 2003;James, 2003;Eddaoudi et al, 2002;Ruben et al, 2005, Kitagawa et al, 2004.…”