Authors:
Chinnasamy Selvakkumar1*, Eashwarwark Vikram Reddy2, Kesavanarayanan Krishnan Selvarajan3, Nazeerullah Rahamuthullah1 and Muftha Mohamed Zarmouh1
1Department of Microbiology and Immunology, Faculty of Medicine, Misurata University, Libya
2Department of Microbiology, Sri Lakshmi Narayana Institute of Medical Sciences, Bharath University, Puducherry, India
3Department of Pharmacology, SRM College of Pharmacy, SRM University, Chennai, India
Received: 03 March, 2016; Accepted: 26 April, 2016; Published: 04 May, 2016
Dr. Chinnasamy Selvakkumar, Department of Microbiology and Immunology, Faculty of Medicine, Misurata University, Libya, E-mail:
Selvakkumar C, Reddy EV, Selvarajan KK, Rahamuthullah N, Zarmouh MM (2016) Design of Peptide Models for β-Hairpins and Equilibrating Helix-Hairpin Structures. Int J Nanomater Nanotechnol Nanomed 2(1): 015-017. DOI: 10.17352/2455-3492.000009
© 2016 Selvakkumar C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction
It is well established that synthetic peptides containing a centrally positioned Type-I or Type-II β-turn can form well folded peptide hairpins (1). Earlier studies from this laboratory have established that D-Pro-Xxx segments nucleate β-hairpin structures, with formation of a central Type-II β-turn (2). The octapeptide (Boc-Leu-Phe-Val-Aib-D-Ala-Leu-Phe- Val-OMe) is a rare example of a synthetic peptide hairpin, containing a central Type-I β-turn. Hairpins with Type-I turns are considerably more twisted than their Type-II counterparts. The Aib-Xxx segment has also been shown to adopt a Type-I β-turn structure, resulting in incorporation into the centre of a long synthetic, helical peptide (3) (Figures 1,2).
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Figure 1:
Figure 2:
This observation prompted further studies on the context dependent conformational preferences of -Aib-Xxx- segments, where Xxx = Aib, L-Ala, Gly, D-Ala. It was anticipated that the –Aib-Gly- and –Aib-D-Ala- containing peptides would also provide models for equilibration between well folded, helical and hairpin structures [1-7] (Figure 3).
Figure 3:
The following sequences Boc-Leu-Phe-Val-Aib-Xxx-Leu-Phe-Val-OMe have been chosen for further study.
(1) Boc-Leu-Phe-Val-Aib-Aib-Leu-Phe-Val-OMe
(2) Boc-Leu-Phe-Val-Aib-DAla-Leu-Phe-Val-OMe
(3) Boc-Leu-Phe-Val-Aib-LAla-Leu-Phe-Val-OMe
(4) Boc-Leu-Phe-Val-Aib-Gly-Leu-Phe-Val-OMe
In addition smaller fragments are also being investigated to probe structure formation in the presence of a smaller number of internal (cross-strand) hydrogen bonds.
(5) Boc-Aib-D-Ala-NHMe
(6) Boc-Val-Aib-D-Ala-Leu-NHMe
(7) Boc-Phe-Val-Aib-D-Ala-Leu-Phe-NHMe
(8) Boc-Aib-Aib-NHMe
(9) Boc-Val-Aib-Aib-Leu-NHMe
(10) Boc-Phe-Val-Aib-Aib-Leu-Phe-NHMe
In the crystalline β-hairpin structure of the octapeptide shown in Figure 2, of the four anticipated cross-strand hydrogen bonds in an idealized β-hairpin, the terminal interaction Leu (1) NH--OC Val (8) is disrupted by a large re-orientation about the Cα--CO bond of Val (8) (ψ = -57.3º). Such fraying at hairpin termini is not uncommon.
The target peptides are being synthesized by solution phase procedures and characterized by NMR Spectroscopy. In addition, single crystals have been obtained for peptide sequence that Boc-Val-Aib-DAla-Leu-NHMe and Boc-Val-Aib-Aib-Leu-NHMe and related peptides highly important in vaccine development [8-13].
Experimental section
Peptides synthesis has been undertaken by standard solution phase chemistry. A representative scheme is shown in Figure 4. The following sequences have been synthesized and purified by medium pressure liquid chromatography (MPLC), homogeneity established by HPLC and characterized by 1H NMR spectroscopy and mass spectrometer.
Figure 4:
(a) Boc-Val-Aib-D-Ala-Leu-NHMe
(b) Boc-Val-Aib-Aib-Leu-NHMe
(c) Boc-Phe-Val-Aib-D-Ala-Leu-Phe-NHMe
(d) Boc-Aib-D-Ala-NHMe
(e) Boc-Aib-Aib-NHMe
(f) Boc-Phe-Val-Aib-Aib-Leu-Phe-NHMe
The target octapeptides have not yet been completed (Figure 4).
An anticipated diastereomeric hexapeptide Boc-Phe-DVal-Aib-DAla-Leu-Phe-NHMe during the synthesis of the hexapeptide (7) 2 + 4 strategy was followed, involving activation of the C-terminus carboxylated of the Phe-Val dipeptide resulting in racemization, yielding isolable amounts of diastereomeric peptide containing DVal at position 2. The fortunate formation of single crystal permitted a structure determination which established the configuration at DVal relative to other amino acids in sequence. The observed structure and relevant parameters in the Figures 5a-5e.
Figure 5a:
Figure 5b:
Figure 5c:
Figure 5de:
Unlike protein amino acids, the designed peptide sequence has been synthesized complete non-protein amino acid which is one of the non-coding amino acid in protein synthesis. Moreover this amino acid well known to be nucleating α-helix in designed peptides. The assigned proton NMR spectra have been shown above. The crystal grew by MeOH/CHCl3 solvent system at room temperature by slow evaporation method (Figure 5f).
Figure 5f:
The characteristic 1D proton NMR spectra were shown. Approximately, Proton 1D spectrum can be assigned the backbone of the Cα-H protons, amide groups of N-H protons and side chain of aromatics so. But interest motivated towards crystallization of the peptides. The crystal set up is carried by different kind of solvent medium but the crystal growth not obtained yet. The above said peptides no interaction biding with metal ions due to hydrophobic interactions.
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