Y dipeptides

Fig. 2.38 sheet forming y-peptides. (A) Crystal structure of the two stranded antiparallel sheet formed by a,j -unsaturated y-dipeptide 152 with a-methyl substituted residues [208], Both intermolecular H-bonds are characterized by a N---0 distance of 2.84 A and an angle (N-H- -O) ofl54.2°. (B) Crystal structure of the infinite parallel sheet arrangement formed by vinylogous dipeptide 153 [208], Intermolecular H-bonds are characterized by a N -O distance of 2.88 A and 3.24 A and an... 

On this basis (see Fig. 2.41), various y9-di- and tetra-peptides incorporating [f-HLys-yS -HTrp (e.g. 160 [99], 161 [254]) or y9 -HTrp-y9 -HTrp, a-Trp-y9 -Lys [254] sequences as well as y -dipeptides with a Trp side-chain in the y -position for the first residue and a Lys side chain in the y" -position for the second residue (e.g. 

Fig. 2.41 Schematic representation of type II peptides and unlike-y dipeptide illustrating...

A related palladium(O)-catalyzed epimerization of y-aziridinyl-a,P-enoates 244 was also reported by Ibuka, Ohno, Fujii, and coworkers (Scheme 2.60) [43]. Treatment of either isomer of 244 with a catalytic amount of Pd(PPh3)4 in THF yielded an equilibrated mixture in which the isomer 246 with the desired configuration predominated (246 other isomers = 85 15 to 94 6). In most cases the isomer 246 could be easily separated from the diastereomeric mixture by a simple recrystallization, and the organocopper-mediated ring-opening reaction of 246 directly afforded L,L-type (E)-alkene dipeptide isosteres 243. 

Tabata, Y. and Ikada, Y., Activation of macrophage in vitro to acquire antitumor activity by a muramyl dipeptide derivative encapsulated in microspheres composed of lactide copolymer, J Control. Rel.. 6, 189, 1987. 

FIGURE 3 Schematic representation of a pseudopoly (amino acid) derived from the side chain polymerization of a dipeptide carrying protecting groups X and Y. The wavy line symbolizes a nonamide bond. In this polymer, the amino acid side chains are an integral part of the polymer backbone while the termini have become pendant chains. In the backbone, amide and nonamide bonds strictly alternate. 

Lindley proposed an oblique, planar, stereogeometric arrangement between AH,B and y that is strikingly similar to Kier s tripartite glucophore, with distance and direction parameters as shown in Fig. 12. A similar y site for other sweeteners, such as the sweet dipeptides, has also been proposed, and it appears that the location of y in relation to AH,B is directional rather than positional. 

Fig. 12.—Location" of the Third Binding-site in Nitroanilines (X), Sugars (-y), and Dipeptide Sweeteners (S). [Distances given in pm.]...

Oi anic synthesis IS [OS 18] Dipeptide from Fmoc-L-y homophenylalanine... 

Dmab-y0-alanine and Fmoc-L-y homo-j )-chlorophenylalanine were reacted to give the dipeptide [5]. 

Boldyrev, A.A., Dupin, A.M., Bunin, A.Y., Babizhaev, M.A. and Severin, S.E. (1987). The antioxidant properties of carno-sine, a natural histidine containing dipeptide. Biochem. Int. 15, 1105-1113. 

An efficient route for the synthesis of the Phe-Phe hydroxyethy-lene dipeptide isostere precursors utilized for the design of potential inhibitors of renin and HIV-protease was developed. The key step is the zinc-mediated stereoselective allylation of A-protected a-amino aldehydes in aqueous solution (Eq. 8.32).70 NaBF4/M (M = Zn or Sn) showed facilitating allylation of a variety of carbonyl compounds in water, and a-and y-addition products of crotylations could be alternatively obtained under the control of this novel mediator (Eq. 8.33).71... 

Figure 1. Molecular structures of Bisphenol A and fully protected tyrosine dipeptide. The amino and carboxylic acid groups of the dipeptide are rendered unreactive by protecting groups (schematically represented by X and Y). This leaves the phenolic hydroxyl groups as the only reactive sites of the molecule.

Covitz, K.-M. Y., G. L. Amidon, and W. Sadee. Human dipeptide transporter, hPEPTl, stably transfected into Chinese hamster ovary cells. Pharm. Res. 1996, 113, 1631-1634. 

Tomita, Y., et al. Transport of oral cephalosporins by the H+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells. J. Pharmacol. Exp. Ther. 1995, 272, 63-69. 

Patients have metabolic acidosis caused by excessive formation of 5-oxoproline (pyroglutamic acid Fig. 40-6, reaction 2). This occurs because the diminution of intracellular glutathione relieves the feedback inhibition on the y-glutamylcysteine synthetase pathway (reaction 1), thereby augmenting the concentration of y-glutamylcys-teine and the subsequent conversion of this dipeptide to cysteine and 5-oxoproline in the cyclotransferase pathway (reaction 4). 

K Takeda, A Ayabe, M Suzuki, Y Konda, Y Harigaya. An improved method for the synthesis of active esters of A-protected amino acids and subsequent synthesis of dipeptides, (isopropenyl mixed carbonates) Synthesis 689, 1991. 

Figure 10.9 Structure of y-glutamylalanine. The dipeptide consists of glutamic acid linked by a peptide bond which involves the carboxyl group attached to the - carbon atom and the a-amino group of alanine.

The unusual amino acid (S)-2-amino-(Z)-3,5-hexadienoic acid (269), which is a component of the toxic y-glutamyl dipeptide isolated from the defensive glands of the Colorado beetle [209], has been synthesized along Scheme 17, after two initial attempts had proved unsuccessful due to the instability of 269 towards various oxidation conditions [210]. Scheme 17 relies on the hydrolysis of an ortho ester to generate the required carboxylic acid. Thus, the L-serine aldehyde equivalent 270 was treated with ( )-l-trimethylsilyl-l-propene-3-boronate to give the addition product 271. Reaction of 271 with KH gave the stereochemically pure (Z)-diene 272. Mild acid treatment of 272 followed by... 

Some generic structures of /3-amino acids are shown in Fig. 6.40. Since, in /3-amino acids, two C-atoms separate the amino and carboxylate groups, there are two possible locations for attachment of a single side chain (i.e., /32 and /33), or even two or more side chains (e.g., /32,3 and /32,2,3, respectively). In a /3-peptide, these symbols can be used as prefixes, e.g., the /33/32-dipeptide in Fig. 6.40 becomes /33-HAla- /32-HVal for R=Me and R = i-Pr. The stereodescriptors (R) and (S) should be used to specify the absolute configuration at the stereogenic centers. The same rules apply to y-amino acids and y-peptides. 

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