P-tum structure

Scheme 5 Good and Bad Cyclization Sites in Peptides of Known p-Tum Structure...

The nsefnlness of this approach is demonstrated in identifying the secondary structure of methionine enkephalin (YGGFM) [46]. A controversy has persisted in the literature as to whether this peptide forms a 5 -> 2 P-tum or a 4 1 P-tum structure. By acquiring the CID-MS/MS spectrum of the deuterated peptide in a 50% trifluoroethanol-di/D20 solvent mixture, it was revealed that methionine enkephalin forms a 5 2 P-tum structure. 

NMR spectrum of the dragline silk of the C/ N-proline-enriched Argiope aurantia spider, which is rich in MaSp2. However, extensive spectral overlap between Pro and other amino acids, with the exception of the Pro C(x, compromises the extraction of exact chemical shift values. Hence, 13c 13c correlation NMR with a medium 50 ms DARR recoupling period was utilized to exploit the connectivity within the Pro residue to yield precise chemical shifts. A chemical shift difference of 5.1 ppm was found, which was indicative of a type II P-tum structure. This structural assignment was further confirmed by using HETCOR experi-... 

Postsynaptic neurotoxins are composed mainly of an antiparallel (3-sheet and a p-tum structure, with only a small amount of a-helical structure (Yu et al., 1975 Tu, 1990 Betzel et al., 1991 LeGoas et al., 1992 Yu et al., 1990 Tu et al., 1976). The toxin is comprised of three loops. A, B, and C (Fig. 4). Loop B is considered most important, and it is believed that this loop is attached to the acetylcholine-binding site of the AChR. Loop B is also the antigenic determinant. 

Fig. 7 (a) Recurring P-tum found in poly(VPGVG). (b) P-spiral structure adopted by the poly(VPGVG) upon raising the temperature above the inverse transition temperature. Reprinted from [22] with permission from Elsevier, copyright 1992... 

While RNA molecules do not have the double stranded structure usually found in DNA, in many RNA molecules stem-loop structures are found in which the anti-parallel strands are connected by a 5-7 residue loop. Rather like the P-tum in proteins, this allows the... 

Figure 2. Three-dimensional structure of human cytochrome c created by Protein Adviser, ver 3.0 (FQS, Hakata, Japan) with PDB file of human cytochrome c down-loaded from protein structure database of NCBI. a-Helices are shown as purple ribbons, random coils as white strands, and P-tums are blue (see separate colour tip). Heme c is depicted in white straight lines inside the protein.

Substituted 6-aminohexanoic acid linkers were utilized by Aube et al.[159l to enforce either a type-I or type-II p-tum, depending on the substitutents at the R1 to R4 positions, in structure 119 (Scheme 43). 

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. 

In addition, there are many important nonantibiotic uses of 2-azetidinones in fields ranging from enzyme inhibition [15-21] to gene activation [22], Systems containing one carbon atom common to two rings, spirocyclic compounds, represent an important structural organization. Spirocyclic p-lactams (Fig. 3) behave as p-tum mimetics [23-26] as well as enzyme inhibitors [27, 28], they are precursors of a,a-disubstituted p-amino acids [29-32], and the spiranic p-lactam moiety is present in chartellines and chartelamides [33-38], a family of marine natural products. Synthetic studies and biosynthetic speculation inspired by an unexpected reaction on the marine alkaloid chartelline C have been described [38],... 

Among the various strategies available for p-tum mimics, the Freidinger y-lactam structure (1), or a spiro system [144] (2),has been found suitable for the design of a variety of medicinally relevant targets. In addition, it has been recently reported that use of a,a-disubstituted [S-lactam (3) could also be a good approach to promote a p-tum folding in a peptide chain [145] (Fig. 12). 

Many diasteromeric peptides of type (R,S)-27 and (S,S)-28 (Scheme 1) could be crystallized and their absolute configuration determined based on the known ( -configuration of L-phenylalanine. Table 1 shows a compilation of the relevant torsional angles (4>1/ P1) derived from crystal structures of the peptides shown.108 It is interesting to note that the (S,S)-diastereomers show a high prevalence for P-tum type I conformations in the crystal state. 

Since serine shows a high occurrence at the exposed positions (i+1) and (i+2) of P-tums in protein crystal structures,138,185 it was decided to investigate whether or not the (/ )- and (S)- a-chimeras of Asp-Ser would be interesting P-turn mimetics at the (i+Imposition of P-turns. Furthermore, it was of interest to see whether or... 

Beside the classical secondary structure elements occurring at the surface of proteins such as y- and P-tums, 3,0- and a-helices, and P-sheets, loops of variable size seem to play a crucial role in many protein-protein interactions (see Section I.A). Several amino acid-derived templates have been proposed to stabilize P-tums as external templates (see Section II.B) and a compilation of loop-stabilizing templates is shown in Figure 25.189-194... 

Secondary structures are formed by short stretches of residues. These substructures make up sequentially proximal components of proteins, and they have shapes. There are various forms of protein secondary structures, e.g., helices (the most common of which is the a-helix), P-sheets, p-tums, Q-loops, and some that remain unclassifiable and are typically referred to as random coil or loop regions. A complex combination of attractive and repulsive forces between close and more distant parts of the structure affects the resultant shape of secondary structures, and predicting secondary structure from knowledge of the linear amino acid sequence alone remains a tremendous challenge. 

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