Peptides analogues

Two different mixtures of peptides and alkaloids (qv) have been analy2ed by ce/uv/ms using sims to determine whether this technique can detect trace impurities in mixtures (85). The first mixture consisted of two bioactive peptide analogues, which included Lys-bradykinin (kahidin) and Met-Lys-bradykinin. The presence of 0.1% Lys-bradykinin was detected by sim ce/ms but not by ce/uv at 0.1% level as it migrated from the capillary column prior to the main component, Met-Lys-bradykinin. The second mixture consisted of two antibacterial alkaloids, berberine and palmitine. The presence of 0.15% palmitine was detected by ce/uv and sim ce/ms at 0.15% level as it migrated from the capillary column, following the main component berberine. This technique can provide a complementary technique for trace components in such sample mixtures. 

Application of the concept of conformational restriction to opioid peptides has produced fruitful results, insofar as peptide analogues and mimetics with interesting opioid activity profiles and high stability against enzymatic... 

Schiller PW, Weltrowska G, Nguyen TM-D, Lemieux C, Chung NN, Marsden BJ, Wilkes BC. Conformational restriction of the phenylalanine residue in a cyclic opioid peptide analogue effects on receptor selectivity and stereospecificity. J Med Chem 1991 34 3125-3132. 

Corbett AD, Gillan MGC, Kosterlitz HW, McKnight AT, Paterson SJ, Robson LE. Selectivities of opioid peptide analogues as agonists and antagonists at the 6-receptor. Br J Pharmacol 1984 83 271-279. 

Head-Gordon, T., M. Head-Gordon, M. J. Frisch, C. L. Brooks EH, and J. A. Pople. 1991. Theoretical Study of Blocked Glycine and Alanine Peptide Analogues. J. Am. Chem. Soc. 113, 5989-5997. 

Viviana, W., J.-L. Rivail, and I. G. Csizmadia. 1993a. Peptide Models n. Intramolecular Interactions and Stable Conformations of Glycine, Alanine, and Valine Peptide Analogues. Theor. Chim. Acta 85,189-197. 

Octreotide -synthetic peptide analogue of somatostatin -abdominal pain, nausea, vomiting, diarrhea -local injection site reactions -cholelithiasis -sweating, flushing -hyperglycemia (many patients will require insulin therapy)... 

Fig. 1 Solid-state NMR structure analysis relies on the 19F-labelled peptides being uniformly embedded in a macroscopically oriented membrane sample, (a) The angle (0) of the 19F-labelled group (e.g. a CF3-moiety) on the peptide backbone (shown here as a cylinder) relative to the static magnetic field is directly reflected in the NMR parameter measured (e.g. DD, see Fig. 2c). (b) The value of the experimental NMR parameter varies along the peptide sequence with a periodicity that is characteristic for distinct peptide conformations, (c) From such wave plot the alignment of the peptide with respect to the lipid bilayer normal (n) can then be evaluated in terms of its tilt angle (x) and azimuthal rotation (p). Whole-body wobbling can be described by an order parameter, S rtlo. (d) The combined data from several individual 19F-labelled peptide analogues thus yields a 3D structural model of the peptide and how it is oriented in the lipid bilayer...

The first step in a strict hierarchical procedure for transforming peptide lead sequences into promising non-peptide analogues generally utilizes the incorpo-... 

Based on the CAAX motif, peptide analogues were designed in which peptide amide bonds are replaced by amine and ether groups [18]. In particular /I-turn mimetic 1 (Fig. 1) inhibits the FTase in vitro with an IC50 value of 1.8 nmol/1 and shows highly specific activity in comparison to inhibition of GGTase I. 

JT Lobl, L Maggiore. Convenient synthesis of C-terminal peptide analogues by aminolysis of oxime resin-linked protected peptides. J Org Chem 53, 1979, 1988. 

N. A. Malik, G. M. Anatharamaiah, A. Gawish, and H. C. Cheung, Structural and biological studies on synthetic peptide analogues of a low-affinity calcium-binding site of skeletal troponin C, Biochim. Biophys. Acta 911, 221-230 (1987). 

The luteinizing hormone releasing hormone antagonist RS-26306 (Fig. 6.19) is another example of a peptide analogue that undergoes hydrolysis of its terminal CONH2 group. This decapeptide contains five synthetic amino... 

Whereas peptidomimetics are sometimes taken to include all types of peptide analogues discussed in this Sect. 6.6, we restrict the term to two types of compounds. The first type includes moieties that mimic some elements of secondary structure, whereas the second type of peptidomimetics are mimics of a peptide s pharmacophore. 

Whereas peptidomimetics are sometimes taken to include all types of peptide analogues discussed in Sect. 6.6, we restrict the term to compounds,... 

Proteins (e.g., modified plasma proteins, lysozyme, synthetic peptides, or peptide analogues) [260 - 262] ... 

Janssen EM. van Oosterhout AJ, van Rensen AJ. van Eden W. Nijkamp FP. Wauben MH Modulation of Th2 responses by peptide analogues in a murine model of allergic asthma amelioration or deterioration of the disease process depends on the Thl or Th2 skewing characteristics of the therapeutic peptide. J Immunol 2000 164 580-588. 

Wharton SA, Martin SR, Ruigrok RW, et al. Membrane fusion by peptide analogues of influenza virus haemagglutinin. J Gen Virol 1988 69(Pt 8) 1847-1857. 

It has been reported by Patel and Gordon " that SPPS is limited by poor yields with hindered amines, deactivated aromatic aldehydes and slight over alkylation with aliphatic aldehydes. Johnson et al argued that because of the speed and convenience of automated SPPS, support-bound cyclization protocols are ideal for the preparation of numerous cyclo peptide analogues. 

A comprehensive review of receptor selective opioid peptide analogues by Schiller [7] appeared in the previous volume of this Series and for this reason the present chapter describes only non-peptide structures. A leading review which introduces kappa opioid analgesics was written by Horwell in 1988 [8] and a subsequent article focusing on kappa receptors and analgesia by Millan appeared in 1990 [9]. 

Phosphonamidate peptide analogues mimicking the P1...F3 substrate residues have been prepared and evaluated against a CHC mixture Table 8.5). Inhibitors with an aromatic side-chain in subsite P] are some 20-fold more effective than are those with an aliphatic one (compare (31) to (29) or (30), Table 8.S). An opposite, albeit less pronounced, preference at this site appears to exist for the ketone inhibitors for fi-CYlC ((17) vs. (25) and (21) vs. (26), Table 8.4). However, this difference could be attributable to a predominance of class II CHC in the mixture assayed in Table 8.5. Thus, comparisons of this sort must be made with caution. Introduction of a double bond into the Pi side-chain decreases the potency of the phosphonamidate by more than a factor of 10 ((41) vs. (42), Table 8.5), perhaps because of... 

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