Peptide, cyclic

Natural Lactones and Lactams Synthesis, Occurrence and Biolo al Activity, First Edition. 

Cyclic peptide Source of Isolation Bioactivity Total synthesis 

Phakellistatin 3 2a, Phakdlia carieri [13] Phakellistatin 3 inhibits Greenman et al. [15] 

Cyclotheonamides Theonella [16] Potent serine protease Wasserman and 

Scleritodermin A 4 Sderitoderma nodosum Activity against a panel Serra etal. [19] and 

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The second application of the CFTI protocol is the evaluation of the free energy differences between four states of the linear form of the opioid peptide DPDPE in solution. Our primary result is the determination of the free energy differences between the representative stable structures j3c and Pe and the cyclic-like conformer Cyc of linear DPDPE in aqueous solution. These free energy differences, 4.0 kcal/mol between pc and Cyc, and 6.3 kcal/mol between pE and Cyc, reflect the cost of pre-organizing the linear peptide into a conformation conducive for disulfide bond formation. Such a conformational change is a pre-requisite for the chemical reaction of S-S bond formation to proceed. The predicted low population of the cyclic-like structure, which is presumably the biologically active conformer, agrees qualitatively with observed lower potency and different receptor specificity of the linear form relative to the cyclic peptide. 

Jorgensen, W.L. Tirado-Rives, J. The OPLS potential functions for proteins. Energy minimizations for crystals of cyclic peptides and crambin. J. Am. Chem. Soc. 110 1657-1666, 1988... 

Enniatin A [11113-62-5] M 681.9, m 122-122.5", [a]Jj -92 (c 0.9, CHCI3). A cyclic peptidic ester antibiotic which is recrystd from EtOH/water but is deactivated in alkaline soln. [Ovchinnikov and Ivanov in The Proteins (Neurath and Hill eds) Academic Press, NY, Vol V pp. 365 and 516 7952.]... 

The OPLS Potential Function for Proteins. Energy Minimization for Crystals of Cyclic Peptides and Crambin William L. Jorgensen and Julian Tirado-Rives Journal of the American Chemical Society 110 (1988) 1657... 

Antitumor compounds, among them cyclic peptides, terpenoids, and alkaloids isolated from higher plants 99YZ529. 

Chemical synthesis of natural cyclic peptides 97CRV2243. 

Studies on the synthesis of vancomycin and related cyclic peptides 98PAC391. 

Imanishi, Y. Synthese, Conformation, and Reactions of Cyclic Peptides. Vol. 20, pp. 1 — 77. Inagaki, H. Polymer Separation and Characterization by Thin-Layer Chromatography. Vol. 24, pp. 189-237. 

Imanishi, Y. Syntheses, Conformation, and Reactions of Cyclic Peptides. Vol. 20, pp. 1-77. 

Phalloidin and phallacidin are cyclic peptides from the mushroom Amanita phalloides that stabilize F-actin. Phalloidin binds to residues 114-118 of an actin protomere and blocks nucleotide exchange without interfering with nucleotide hydrolysis. It enhances the rate of nucleation as well as that of elongation. It slowly penetrates the cell membrane and is used for immunocytochemical localization of F-actin. 

Cyclosporine A (CsA) is a water-insoluble cyclic peptide from a fungus composed of 11 amino acids. CsA binds to its cytosolic receptor cyclophilin. The CsA/cyclophilin complex reduces the activity of the protein phosphatase calcineurin. Inhibition of this enzyme activity interrupts antigen receptor-induced activation and translocation of the transcription factor NEAT to the nucleus which is essential for the induction of cytokine synthesis in T-lymphocytes. 

Somatostatin is a regulatory cyclic peptide, which has originally been described as a hypothalamic growth hormone release-inhibiting factor. It is produced throughout the central nervous system (CNS) as well as in secretoty cells of the periphery and mediates its regulatory functions on cellular processes such as neurotransmission, smooth muscle contraction, secretion and cell proliferation via a family of seven transmembrane domain G-protein-coupled receptors termed sstx 5. 

Cyclic peptide from 11 amino acids. Preparation by fermentation of Tolypocladium inflatum Gams with addition of DL-a-aminobutyric acid to the fermentation medium. Isolation by homogenization of mycelium, extraction with 90 % methanol and column chromatographic purification. 

A considerable number of mycotoxins that show high toxicity to vertebrates and/ or invertebrates are produced by organisms associated with crop plants (Flannigan 1991). There are many known cases of human poisoning caused by such compounds. There are three broad categories of mycotoxins represented here, based on the structures of the intermediates from which these secondary metabolites are derived. They are (1) compounds derived from polyketides, (2) terpenes derived from mevalonic acid, and (3) cyclic peptides and derivatives thereof. 

Fig. 6.9 Dinuclear Zn(ll) complex of cyclic decapeptide as reported by Ka-wai et al. [53] modeled after the iono-phoric cyclic peptide gramicidin S and active in the cleavage of HPNP...

Further, Wasserman and coworkers developed a direct acylation of stabilized phosphonium ylides by carboxylic acids in presence of the EDCI/DMAP (way c). This last method allows the introduction of a-aminoacid structures into the resulting P-oxo phosphorus ylides [19-25],opening the way to the total synthesis of depsipeptide elastase inhibitors [22,24] or cyclic peptidic protease inhibitor EurystatinA [20]. 

Dutton reported on the synthesis of an e-caprolactam analog of an anthelmintic cyclic peptide. The a-hydroxy-e-caprolactam 44 was generated in an ex chiral pool synthesis staring from malic acid. The a-hydroxy carboxylic acid unit was protected as a dioxolanone in 43. The protective group served simultaneously as the reactive function during cyclization lactam 44 formation succeeded by ring opening of the dioxolanone 43 by the nucleophilic attack of the amino function, Eq. (8) [14]. 

Finally, the chiral auxiliary was removed by a Birch reduction or a catalytic hydrogenation. After ring opening several optically active 6-aminohexanoic acids served as linkers in cyclic peptides as /1-turn mimetics (Table 12, Scheme 49) [51c],... 

Urotensin II Receptor (GPR14). The vasoactive cyclic peptide urotensin II (U-II) is the endogenous ligand of the G protein-coupled orphan receptor GPR14. Structure-activity relationships from 25 peptide analogs, which mobilize intracellular calcium in GPR14-transfected CHO cells, and the... 

The cellular/molecular mechanism of action for these cyclic peptide toxins is now an area of active research in several laboratories. These peptides cause striking ultrastructural changes in isolated hepatocytes (95) including a decrease in the polymerization of actin. This effect on the cells cytoskeletal system continues to be investigated and recent work indirectly supports the idea that these toxins interact with the cells cytoskeletal system (86,96). Why there is a specificity of these toxins for liver cells is not clear although it has been suggested that the bile uptake system may be at least partly responsible for penetration of the toxin into the cell (92). 

A saponin-like substance, agelasine, was isolated from Agelas dispar (10). Suber-itine from Suberites domcunculus was originally isolated by Richet (32) and was shown to be heat labile and have a MW of 28,000 by Cariello et al. (33). A cyclic peptide, dolastin, was isolated from Dolabella awicularia (34). 

Figure 32 Adamantane-containing norbornene ( i )-constrained cyclic peptides possess the ability to transport ions across the model membranes in both specific and nonspecific ways [162].

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