Cyclic peptide analogs

T140 [101]. Further optimization has led to identification of additional potent small cyclic peptide analogs [102],... 

In cases where peptides contained either aliphatic hydroxy (Ser or Thr) or carboxy groups (Asp or Glu, or free a-carboxy), a second deformylation procedure was employed 30 To the cyclic peptide analogous to 5 was added hydrazine monohydrate (99%, 5.4 mL, 111 mmol) in EtOH/H20/AcOH (55 35 10, 45 mL) with stirring. The mixture was kept at 37 °C for 16 h after which time completion of the deformylation was verified by analytical RP-HPLC. 

BY Cho, R Strong, IS Krull. HPCE of a fermentation derived, cyclic peptide analog, animal growth promotor. J Chromatography. B, 697 163-174, 1997. 

Nozaki S, Muramatsu 1. Natural homologs of gramicidin S. J Antibiot 1987 37 689-690. Thibault P. Faubert D, Kaiunanirhy S, Boyd RK. Holmes CFB. Isolation, mass spectromctric characterization, and protein phosphatase inhibition properties of cyclic peptide analogs ol gramicidin S from Bacillus brevis (Nagano strain). Biol Mass Spectiom 1992 21 367—379. 

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]. 

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... 

Schiller PW, Nguyen TM-D, Maziak LA, Lemieux C. A novel cyclic opioid peptide analog showing high preference for p-receptors. Biochem Biophys Res Commun 1985 127 558-564. 

Wilkes BC, Schiller PW. Theoretical conformational analysis of a p-selective cyclic opioid peptide analog. Biopolymers 1987 26 1431-1444. 

The widespread occurrence of cyclic peptides and depsipeptides in natura makes the research on the development of rapid and efficient approaches for their generation mandatory. The rational design of synthetic cycfic peptide analogs, focused on biological activities that imitate natural structural motifs (turns, hefices, etc.), can help to increase their native properties and to adapted them for human applications, for example, in medicine [12-14]. 

Fig. 6 cyclic peptides as reversible and irreversible HDAC inhibitors. (Chlamydocin San-doz AG CHAP 1 Univ. of Tokyo Apidicin Merck Co reversed hydroxamic acid analogs of Cyl-1 Kyushu Institute of Technology and Japan Science and Technology Agency)... 

Cyclic peptides are of interest as turn mimetics or as conformationally constrained peptide analogs. The cyclization of peptides can either be performed after cleavage from the support in solution (see, e.g. [58]) or while still on the support. Besides cycli-zations of the peptide backbone, peptides can be cyclized through their side chains or by means of a non-natural spacer. To cyclize the backbone of a peptide on an insoluble support, the peptide must be attached to the support either by a backbone amide linker [59] or via the side chain of an amino acid [60] (Figure 16.7). 

Analogs of cyclic peptides have been prepared using a variety of spacers and reaction conditions to achieve the macrocyclization. These include olefin metathesis (Section 5.2.3), nucleophilic substitution (Sections 8.2 and 7.2.3), and the Heck reaction [82]. 

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