Conformations in the Solid State and Solubility Properties of Protected Homooligopeptides of Glycine and β-Alanine

Narita, Minoru; Doi, Masamitsu; Kudo, Koji; Terauchi, Yasuhiro

doi:10.1246/bcsj.59.3553

Cited by 36 publications

(19 citation statements)

References 22 publications

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“…Substitution with rigidifying residues such as D-Ala, Aib, or Pro does not lead to analogues endowed with outstanding activity and/or selectivity. Surprisingly, substitution of Gly8 in NKA(4-10) with the more flexible /3-Ala8 residue (Salunke & Vijayan, 1984; Narita et al, 1986) leads to an analogue that is more active than the parent compound and, even more important, is the synthetic tachykinin with the highest known selectivity for the NK-2 receptor (Rovero et al, 1989b). These results pose the question whether the [/3-Ala8]NKA(4-10) molecule, as a whole, is indeed more flexible than NKA(4-10), a fact that is difficult to reconcile with selectivity.…”

mentioning

confidence: 99%

Conformation-activity relationship of tachykinin neurokinin A(4-10) and of some [Xaa8] analogs

Saviano¹,

Temussi²,

Motta³

et al. 1991

Biochemistry

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NKA (4-10), the C-terminal heptapeptide fragment (Asp-Ser-Phe-Val-Gly-Leu-Met-NH2) of tachykinin NKA, is more active than the parent native compound in the interaction with the NK-2 receptor. Substitution of Gly8 with the more flexible residue beta-Ala8 increases its selectivity with respect to other two known receptors (NK-1 and NK-3), whereas substitution with either D-Ala8 or GABA8 deprives the peptide of its biological activity. These findings can be interpreted by a conformational analysis based on NMR studies in DMSO-d6 and in a DMSO-d6/H2O cryoprotective mixture combined with internal energy calculations. NKA(4-10) is characterized by a structure containing a type I beta-turn extending from Ser5 to Gly8, followed by a gamma-turn centered on Gly8, whereas for [beta-Ala8]NKA(4-10) is possible to suggest a type I beta-turn extending from Ser5 to beta-Ala8, followed by a C8 turn comprising beta-Ala8 and Leu9 and by another beta-turn extending from beta-Ala8 to the terminal NH2. The preferred conformation of [beta-Ala8]NKA(4-10) is not compatible with models for NK-1 and NK-3 agonists proposed on the basis of rigid peptide agonists [Levian-Teitelbaum et al. (1989) Biopolymers 28, 51-64; Sumner & Ferretti (1989) FEBS Lett. 253, 117-120]. The preferred solution conformation of [beta-Ala8]NKA(4-10) may thus be considered as a likely bioactive conformation for NK-2 selective peptides.

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mentioning

confidence: 99%

Conformation-activity relationship of tachykinin neurokinin A(4-10) and of some [Xaa8] analogs

Saviano¹,

Temussi²,

Motta³

et al. 1991

Biochemistry

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“…The residue was recrystallized from ethyl acetate and heptane to give dipeptide 2 as colorless crystals (11.4 Boc-(b-Ala) 4 -OBzl (3): This compound was prepared previously by a similar method. [45] Boc-b-Ala-b-Ala-OBzl (2) (3.52 g, 10.0 mmol) was added to a mixture of TFA and CH 2 Cl 2 (1:1, 10 mL) at 0 8C and the reaction mixture was stirred for 1 h at 0 8C and additionally for 1 h at room temperature. The solvent was evaporated and b-Ala-b-Ala-OBzl·TFA was obtained and used without further purification.…”

Section: Resultsmentioning

confidence: 99%

Cyclic β‐Tetra‐ and Pentapeptides: Synthesis through On‐Resin Cyclization and Conformational Studies by X‐Ray, NMR and CD Spectroscopy and Theoretical Calculations

Büttner¹,

Norgren²,

Zhang³

et al. 2005

Chemistry A European J

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The solution-phase synthesis of the simplest cyclic beta-tetrapeptide, cyclo(beta-Ala)4 (4), as well as the solid-phase syntheses through side chain anchoring and on-resin cyclization of the cyclic beta3-tetrapeptide cyclo(-beta3hPhe-beta3hLeu-beta3hLys-beta3hGln-) (14) and the first cyclic beta3-pentapeptide cyclo(-beta3hVal-beta3hPhe-beta3hLeu-beta3hLys-beta3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(beta-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo-beta3-tetrapeptide causes stabilization of one dominating conformer. The cyclic beta3-pentapeptide on the other hand shows larger conformational freedom. The X-ray structure of achiral cyclo(beta-Ala)4 (4) displays a Ci-symmetrical 16-membered ring with adjacent C=O and N-H atoms pointing pair wise up and down with respect to the ring plane. CD spectroscopic examinations of all cyclic beta-peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities.

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“…Exxon Butyl 268 (i.e., 1 ) was donated by Vanderbilt Chemicals. Oligo(β-alanine)s were synthesized following a solution-phase peptide coupling procedure …”

Section: Methodsmentioning

confidence: 99%

“…Oligo(β-alanine)s were synthesized following a solutionphase peptide coupling procedure. 52 Chemical Structure Characterization. NMR measurements were performed on a Varian Mercury 300 MHz or Varian Avance 500 MHz instrument.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Supramolecular Elastomers. Particulate β-Sheet Nanocrystal-Reinforced Synthetic Elastic Networks

Scavuzzo

Zhao

et al. 2016

Macromolecules

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β-Sheet crystals in natural silks are particulate and less than 10 nm in size in all three dimensions. In synthetic supramolecular analogues of natural silks, β-sheet crystals have been found to be fibrous with the longest dimension exceeding 100 nm in the hydrogen-bonding direction. This work demonstrates that particulate β-sheet crystals can be achieved without the use of an elaborate amino acid sequence by simply grafting oligo(β-alanine) segments as pendent side groups to a butyl rubber main chain. The size control in the hydrogen-bonding direction is attributable to an entropic force that opposes the driving force for the self-assembly. The nanocrystals, especially those of trimeric β-alanine segments, display a remarkable ability to simultaneously provide stiffness, extensibility, and strength to the synthetic elastic network and do so highly efficiently at a low volume fraction of the material. The herein studied butyl rubber-based thermoplastic elastomers containing no more than 3.6 vol % of β-sheet nanocrystals are stiffer, stronger, and more extensible than vulcanized butyl rubber reinforced by 20 vol % of carbon black and poly(styrene-b-isobutylene-b-styrene) reinforced by >33 vol % of polystyrene domains. The high reinforcing efficacy of the β-sheet crystals is attributable to two phenomena associated with their small sizes: a stick–slip mechanism for energy dissipation and an auxiliary layer of polymer brush that contributes to increasing the modulus.

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Conformations in the Solid State and Solubility Properties of Protected Homooligopeptides of Glycine and β-Alanine

Cited by 36 publications

References 22 publications

Conformation-activity relationship of tachykinin neurokinin A(4-10) and of some [Xaa8] analogs

Conformation-activity relationship of tachykinin neurokinin A(4-10) and of some [Xaa8] analogs

Cyclic β‐Tetra‐ and Pentapeptides: Synthesis through On‐Resin Cyclization and Conformational Studies by X‐Ray, NMR and CD Spectroscopy and Theoretical Calculations

Supramolecular Elastomers. Particulate β-Sheet Nanocrystal-Reinforced Synthetic Elastic Networks

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