A combined extended and helical backbone for Boc‐(Ala‐Leu‐Ac₇c‐)₂‐OMe^*

Abstract

The structure of the peptide Boc-Ala-Leu-Ac7c-Ala-Leu-Ac7c-OMe (Ac7c,1-aminocycloheptane-1-carboxylic acid) is described in crystals. The presence of two Ac7c residues was expected to stabilize a 3(10)-helical fold. Contrary to expectation the structural analysis revealed an unfolded amino terminus, with Ala(1) adopting an extended beta-conformation (Phi=-93 degrees, psi=112 degrees). Residues 2-5 form a 3(10)-helix, stabilized by three successive intramolecular hydrogen bonds. Notably, two NH groups Ala(1) and Ac7c(3) do not form any hydrogen bonds in the crystal. Peptide assembly appears to be dominated by packing of the cycloheptane rings that stack against one another within the molecule and also throughout the crystal in columns.

Cyclooxygenase‐2 expression in medullary thyroid carcinoma

“…In this section, we show how the concept of kernels allows for accurate calculation of peptide energy. All of their crystal structures are known 9–19 and have been used in the energy calculations presented here. Table II illustrates a variety of natural and synthetic peptides which vary in size, shape, and function.…”

“…ISARAM and ISARIAX 13 are cyclic rings, containing several unusual amino acid residues and displaying both strong and weak intermolecular H‐bonds. ALAC7 14 is a peptide characterized by packing of cycloheptane rings that stack against one another within the molecule and, throughout its crystal structure in columns. BHLV8 15 incorporates β‐hairpins generated from hybrid peptide sequences containing both α and β amino acids.…”

Helical screw‐sense preferences of peptides based on chiral, Cα‐tetrasubstituted α‐amino acids

“…Interestingly, even if the saturated cycloheptane ring of Ac 7 c is more flexible than the binaphthyl‐fused ring of Bin, and in 9 out of the 24 crystallographically documented Ac 7 c occurrences in N‐acylated derivatives and peptides one or more ring atoms are disordered over two positions, we found an intriguing relationship between backbone helical screw‐sense and side‐chain torsion angles. Specifically, in the absence of ring disorder, in 9 out of 10 examples of the right‐handed helical Ac 7 c residues, the χ 1,1 torsion angle involving the pro ‐( S ) C γ atom is trans , while χ 1,2 is g + with values comprised between +74° and +93°.…”

Crystal structure of a tripeptide containing aminocyclododecane carboxylic acid: a supramolecular twisted parallel β-sheet in crystals

“…Tetrasubstitution at the C α atom (C α,α ‐dialkylated amino acids) has been shown to reduce the inherent flexibility of peptide chains , thus facilitating the process of crystallization. Incorporation of C α,α ‐dialkylated amino acids such as α‐aminoisobutyric acid and its analogues in polypeptide sequences has enabled the structural characterization of major secondary structural elements of proteins in medium sized peptides and has provided information which are useful in designing higher levels of protein structures . Extensive studies on C α,α ‐dialkylated amino acid residues with both linear and cycloalkyl side chains have revealed that they favor helical or β‐turn conformations .…”

“…Incorporation of C α,α ‐dialkylated amino acids such as α‐aminoisobutyric acid and its analogues in polypeptide sequences has enabled the structural characterization of major secondary structural elements of proteins in medium sized peptides and has provided information which are useful in designing higher levels of protein structures . Extensive studies on C α,α ‐dialkylated amino acid residues with both linear and cycloalkyl side chains have revealed that they favor helical or β‐turn conformations . 1‐Amino‐cycloalkane‐1‐carboxylic acid, Ac n c, (where n is the number of atoms in the cycloalkane side chain) with ring sizes (n) varying from 3 to 12 had been incorporated in synthetic peptides and been structurally characterized .…”