ISSN:
0006-3525
Keywords:
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The peptide design using α,β-dehydro-residues has wide applications. To design an extensive 3 10-helical conformation, a heptapeptide Boc-L-Val-ΔPhe-ΔPhe-L-Val-ΔPhe-ΔPhe-L-Val-OCH3 with a repeat of two consecutive ΔPhe residues has been synthesized using an azlactone method in solution phase. This is the first design using a repeat of two consecutive ΔPhe residues. It is observed that the ΔPhe in a sequence of two consecutive ΔPhe residues, adopts only one set of φ,ψ values, i.e., ±60°, ±30°, thus making it a specific design tool. The peptide crystallized from its solution in a methanol-water mixture in the space group P21 with a = 10.159(5)A, b = 20.057(2)A, c = 14.448(3)Å, β = 99.41(2)°, V = 2904(2)Å.3 The structure has been determined by direct methods and refined to an R value of 0.048 for 5404 observed [I ≥ 3 δ(I)] reflections. The structure consists of a heptapeptide Boc-L-Val-ΔPhe-ΔPhe-L-Val-ΔPhe-ΔPhe-L-Val-OCH3 and a solvent methanol molecule in the asymmetric unit. All peptide units in the structure are trans. As a result of six overlapping type III β-turns formed involving seven residues and five intramolecular 4 → 1 hydrogen bonds, the peptide adopts a right-handed 3 10-helical conformation with more than two complete helical turns. It is noteworthy that starting from the Boc group to the C-terminal residue of Val, the 310-helical structure is maintained well. The carbonyl oxygen atom of the Boc group is the first acceptor whereas the carbonyl oxygen atom of Val4 is the last acceptor in the helical structure of the peptide. The side chains of four ΔPhe residues in this helical arrangement exists in a slightly staggered arrangement. The solvent methanol molecule interacts through its hydroxyl group and forms two intermolecular hydrogen bonds, one as a donor with a C-terminal CO group and ΔPhe6 and second as an acceptor with the NH group of ΔPhe2 from the N-terminal region of the peptide. Thus the solvent molecule plays a significant role in promoting a head-to-tail packing of 310-helices of the peptide. There are no lateral hydrogen bonds between the helices, but there exist several van der Waals interactions involving the hydrophobic side chains of peptide molecules. © 1997 John Wiley & Sons, Inc.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
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