Helical screw sense of peptide molecules: The pentapeptide system (Aib)4/L-Val[L-(αMe)Val] in the crystal state

Abstract

The crystal‐state preferred conformations of six Nα‐blocked pentapeptide esters, each containing four helicogenic, achiral α‐aminoisobutyric acid (Aib) residues followed by one chiral L‐valine (L‐Val) or Cα‐methyl‐L‐valine [(αMe)Val] residue at the C‐terminus, have been assessed by x‐ray diffraction analysis. In all of the compounds the (Aib)4 sequence is folded in a regular 310‐helical conformation. In the four pentapeptides characterized by the L‐(αMe)Val residue two conformationally distinct molecules occur in the asymmetric unit. Conversely, only one molecule is observed in the asymmetric unit of two pentapeptides with the C‐terminal L‐Val residue. In the L‐Val based peptides the helical screw sense of the (Aib)4 sequence is right‐handed, whereas in the L(αMe)Val analogues both right‐ and left‐handed helical screw senses concomitantly occur in the two crystallographically independent molecules. © 1998 John Wiley & Sons, Inc. Biopoly 46: 433–443, 1998

Conformations of peptides containing a chiral cyclic α, α‐disubstituted α‐amino acid within the sequence of Aib residues

“…Considering these results, both right‐handed and left‐handed helices are present in the equilibrium mixtures of these peptides in solution, and a slightly energetically favorable conformer is preferentially packed in the crystalline state. We conclude that the preference for a given helical handedness governed by side‐chain chiral centers, which affects achiral Aib‐based peptide segments is lower than that of L‐amino acids with an α‐chiral center4.…”

“…It usually has a right‐handed ( P ) screw sense because of the asymmetric center of the α‐carbon of L‐α‐amino acids1. Several studies have attempted to control the helical screw sense of peptides2–10, and we have recently reported that a chiral cyclic α,α‐disubstituted α‐amino acid bearing only side‐chain chiral centers, (3 S ,4 S )‐1‐amino‐(3,4‐dimethoxy)cyclopentanecarboxylic acid [( S , S )‐Ac 5 c dOM ]11 controls the left‐handed ( M ) helical‐screw sense of its homopeptides12. Incidentally, α‐aminoisobutyric acid (Aib) is widely used as a strong helical inducer; however, it does not exhibit a helical‐screw sense bias because Aib is an achiral amino acid13–15.…”

“…Incidentally, α‐aminoisobutyric acid (Aib) is widely used as a strong helical inducer; however, it does not exhibit a helical‐screw sense bias because Aib is an achiral amino acid13–15. Toniolo and Benedetti reported the positional effect of a C α ‐chiral amino acid residue { C α ‐trisubstituted (L‐Val) or C α ‐tetrasubstituted [L‐(αMe)Val: α‐methyl‐L‐valine]} on the screw sense of a preceding and following achiral 3 10 ‐helical sequence composed of Aib residues3, 4. Furthermore, we have reported on the preferred conformations of pentapeptides consisting of one chiral α‐ethylated α,α‐disubstituted α‐amino acid and four Aib residues16.…”

Conformations of helical Aib peptides containing a pair of l‐amino acid and d‐amino acid

“…To date, several studies have attempted to control the helical screw sense of Aib‐based oligopeptides . Furthermore, the screw sense control of helical Aib‐based peptides using a single chiral AA at the N‐terminus or C‐terminus has been investigated in the past decade . Recently, we reported that the hexapeptide Boc‐ l ‐Leu‐ l ‐Leu‐Aib‐ d ‐Leu‐ d ‐Leu‐Aib‐OMe [ tert ‐butoxycarbonyl (Boc), l ‐leucine ( l ‐Leu), d ‐leucine ( d ‐Leu), methyl ester (OMe)], which has two l ‐Leu, two d ‐Leu, and two achiral Aib, could form a left‐handed ( M ) 3 10 ‐helical structure in the crystalline state .…”

Synthesis of Z‐Protected Aib‐ and Phe(2Me)‐Containing Pentapeptides and Their Crystal Structures

“…For the crystalline state, this has been proven by X-ray crystallography (e.g., [21] [22]). In spite of this knowledge, current interest in conformations of small peptides is documented by several recent reports (e.g., for pentapeptides [23] [24]).…”