Cyclic /3-sheet structure

The design and synthesis of cyclic (3-sheet structures is also covered (Section 13.3).[10] Details of synthetic procedures to obtain the cyclic peptides are described (Section 13.3.1) as are considerations of racemization during synthesis and cyclization (Section 13.3.1.1). The remaining parts of this section deal with characterization of cyclic (3-sheet structures (Section... 

Keywords Amphiphilic peptide-lipid interactions Cyclic fS-sheet structure ... 

The template used for generating P-sheet structures described in this section is based on the structure of gramicidin S (1, Scheme 1). Gramicidin S is a head-to-tail cyclic decapeptide discovered over 50 years ago and has the sequence c[-Val-Om-Leu-D-Phe-Pro-]2. 13 The tertiary structure of gramicidin S has since been elucidated and found to exist in a P-sheet/p-turn conformation. 14,15 As shown in Scheme 1, two antiparallel P-strands containing the Val-Om-Leu sequence are held in place by two type II P-tums defined by the D-Phe-Pro sequence. Val and Leu residues occupy H-bonded sites while Orn residues are located in non-H-bonded sites. 

The upper panel of Scheme 1 is the top view of a model of the gramicidin S backbone showing the head-to-tail cyclic nature of the peptide, the positions of the two type IF p-turns, and the positions of the interstrand H-bonds indicated by dashed lines. The p-sheet structure... 

Given the above limitations, however, it is still difficult to predict which sequences will or will not form (3-sheet structures within the context of head-to-tail cyclic (3-sheet scaffolds. Our group has utilized the 14-residue (3-sheet peptide, GSM (2, Scheme 2), as the basis for the studies reported below. GS14 (2) has the sequence c[-VKLKV-d-YPLKVKL-d-YP-] which contains two (3-strands of five residues each, as well as two type II (3-turns. The three-dimensional structure of GS14 (2) determined by NMR is shown in Scheme 2.[16]... 

The increased retention time of the cyclic product is due to the formation of a large hydrophobic preferred binding domain as a consequence of the formation of (1-sheet structure in the peptide (Scheme 2). Removal of side-chain protecting formyl groups with MeOH/HCl for 16 hours results in the formation of a single product 2 with decreased retention time relative to the protected starting material 5 due to reduced hydrophobicity. It is clear that both the cyclization and deformylation reactions proceed smoothly with the quantitative... 

NMR spectroscopic analysis of cyclic peptides has the greatest potential for providing quantitative indication and/or proof of the presence of (3-sheet structure in these molecules. NMR evidence can range from qualitative information from simple one-dimensional experiments to quantitative as well as actual structure determinations from more complex two-dimensional experiments. 

The most definitive proof of p-sheet structure requires the determination of the three-dimensional solution structure of the peptide. For the calculation of such structures one requires the accurate determination of coupling constants by DQF-COSY experiments which give backbone dihedral restraints and through-space connectivities (ROESY or NOESY experiments) which give rise to distance restraints. A combination of these restraints allows the calculation of the three-dimensional structure of the peptide using restrained molecular dynamics simulations. Utilizing this methodology, the three-dimensional structures of a number of cyclic peptides have been solved.[411... 

Several cyclic peptides have between two and eight cysteine residues. They adopt a triple-stranded 3-sheet structure e.g. vertebrate defensins) or a P-hairpin-like structure (e.g thanatin, androctonin, gomesin, and tachyplesin from arthropods and protegrin from vertebrate) or a mixed a-helix/p-sheet conformation (e.g. invertebrate and plant defensins, including some vertebrate defensins). Several reviews have been published in the past years discussing the structure and the mode of action of cyclic AMPs from animals. The reader is referred to the reviews written by Powers and Hancock [108], Bulet et al. [4], Ganz [8], and Yount [88]. In this chapter, only cyclic peptides with a P-hairpin-like structure will be discussed. 

The amino acid sequence 79-93 of VEGF is that involved in the interaction with VEGFR2. Arg-82, Lys-84 and His-86 are key residues in this interaction. The sequence is within a P-sheet structure built with ps and P6 antiparallel strands linked by a type II P-tum. Zilberberg et al. [263] synthesized a 17-amino acid cyclic peptide (cyclo-VEGI) that inhibited binding of VEGF to its receptor in a dose-dependent manner. Cyclo-VEGI... 

Similarly, as shown in Figure 3.21 (b), (c), (d), and (e), there exists an excellent linear correlation between the charge/volume of the charged species encapsulated in the framework and the charge density of the anionic framework for the anionic aluminophosphates with Al/P ratio of 1/2 directed by arylamines, the anionic aluminophosphates with Al/P ratio of 2/3 directed by cyclic amines, the layered anionic aluminophosphates with Al/P ratio of 3/4 and 4,6,8-net topological sheet structure directed by chain-shape alkylamines, and the layered anionic aluminophosphates with Al/P ratio of 3/4 and 4,6,12-net topological sheet structure directed by chain-shape alkylamines as well. 

The efficient role of the seed crystal for inclusion complexation in the solid state is fascinating. Although the mechanism of the role of seed crystals is interesting, it is not easy to clarify. However, as it has been established that molecules in a crystal move quite easily in the solid state [3, 48], easy movement of gaseous molecules into the crystal is understandable. Surprisingly, however, host 12, which has a helical structure with a twofold symmetry axis [20], is converted efficiently into a sheet structure of 82 and a cyclic structure of 83 in the solid state upon contact with ethyl ether vapor in the presence of a seed crystal. 

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