Peptide collection

Even cursory inspection of peptides collected in Table 2.1 provides compelling evidence that the diversity of endogenous peptides is comprised of a much broader set of components than traditional hormones, neuromodulators and antibiotics. In spite of the availability of scattered data on the activity of selected pool components the principal question on the biological role of peptide pools remains unanswered does the bulk of pool peptides represent transient products of protein substrate destmction on their way to reusable amino acid building blocks Or do these peptides perform a useful regulatory function The answer to these questions requires systematic study of a large number of samples in adequate biological test systems. 

Fig. 1. Schematic illustration of a series of constrained cyclic peptides collectively sampling the broad conformational space of a linear analog. The rectangles, triangles, etc. represent organic scaffolds that force peptides into different conformational substates.

The sequencing process consists of the simultaneous measurement of a peptide collection, as shown in Figure 15.14. The sequence is obtained by observation of... 

Tohnachev, V. and Sjoberg, S. 2002. Polyhedral boron compounds as potential linkers for attachment of radiohalogens to targeting proteins and peptides. Collect. Czech. Chem. Commun., 67,913—35. 

Spielvogel, B. R Rana, G. Vyakaranam, K. Grelek, K. Dicke, K. E. Dolash, B. D. Li, S.-J. et al., A novel approach to the syntheses of functionalized, water-soluble icosahedral carboranyl anions. Crystal structure of methyl N-[(trimethylamineboiyl)carbonyl]-L- tyrosinate A synthon for novel carboranyl-peptides. Collect Czech Chem. Commun. 2002, 67, 1095—1108. 

Fig. 3-2. Semipreparative RP-HPLC profile of eyelo(Arg-Lys-X-Pro-X-Ala). The erude sublibrary (160 mol) was dissolved in 0.1 % (v/v) TFA and applied to a Whatman Partisil 10 pm ODS-2 (1 x 50 em) eolumn. The peaks were eluted using a 40-min linear gradient of 0-25 % aeetonitrile in water at a flowrate of 7 mL min . Fractions were collected every 2 min and pooled in three fractions as indicated by arrows 130 pmol of peptides was reeovered (yield 81 %). (Reprinted with permission from ref. [75]. Copyright 1998, Ameriean Chemieal Soeiety.)...

However, the use of a HPLC separation step enabled a remarkable acceleration of the deconvolution process. Instead of preparing all of the sublibraries, the c(Arg-Lys-O-Pro-O-P-Ala) library was fractionated on a semipreparative HPLC column and three fractions as shown in Fig. 3-2 were collected and subjected to amino acid analysis. According to the analysis, the least hydrophobic fraction, which eluted first, did not contain peptides that included valine, methionine, isoleucine, leucine, tyrosine, and phenylalanine residues and also did not exhibit any separation ability for the tested racemic amino acid derivatives (Table 3-1). 

Urodilatin is a peptide similar to atrial natriuretic peptide, which is produced in the distal tubule of the kidney and promotes sodium excretion and diuresis by acting on receptors localized on the luminal site of the collecting duct of the nephron. 

The VACM-1 receptor is a membrane-associated protein with a single putative transmembrane domain that binds selectively AVP (XD — 2 nM), but cannot discriminate between VXR and V2R analogues. It is expressed in endothelial and medullary collecting duct cells and upon stimulation by AVP. It induces a mobilization of cytosolic-free Ca2+, decreases cAMP production and inhibits cellular growth via MAPK phosphorylation and p53 expression. The mechanism of action and physiological functions of this new receptor are not well understood, but it seems to participate in the regulation of AVP induced signal transduction pathways or of a yet unidentified peptide. 

This isoxazolium salt (10 g.) (obtained from the Aldrich Chemical Company, Inc.) was dissolved in 45 ml. of aqueous 1 M hydrochloric acid and reprecipitated by the slow addition with swirling of 400 ml. of acetone. The salt was collected, washed with 300 ml. of acetone, and dried overnight at 25° under reduced pressure (< 1 min.) to give a fluffy product, m.p. 206-208° (decomp.). An isomeric salt, A-ethyl-5-phenylisoxazolium-4 -sulfonate, which may be obtained by the usual synthetic procedure,2 is also useful in peptide synthesis. 

Note Most data collected by Capaldi (1982). Some of the nuclear-coded peptides of complexes I, III, and IV have isoforms which may differ from different tissues. 

Fig. 2.30 Comparison of antiparallel hairpin structures in / -peptides 120-122. (A) / -Pep-tides 120, 121 with a 12-membered R/S dini-pecotic (Nip or/ -HPro) turn segment (gray color). Summary of backbone-backbone and side-chain-side-chain NOEs collected in CD2CI2 and X-ray crystal structure of 121 (stereo-view) [154, 193], The intramolecular H-bond N" 0 distances are shown. The angles (N-H -O) are 170.8° (inner H-bond) and 1 72.3 ° (outer H-bond). (B) jS-Peptide 122 with...

Nodularia spwnigena has also been shown to produce a peptide with hepato-toxic activity. The more recent reports come from Australia (76), the German Democratic Republic (77), Denmark (78), Sweden (79), and Finland (80,81). Recently structure information on Nodularia toxin has been presented by Rinehart (97) for waterbloom material collected in Lake Forsythe, New Zealand, in 1984 by Eriksson et al. (81) from waterbloom material collected in the Baltic Sea in 1986, and Runnegar et al. (82) for a field isolate from the Peel Inlet, Perth, Australia. Structure work by Rinehart, Eriksson, and Runnegar all indicate that the peptide is smaller than the heptapeptide toxins. Rinehart s work (97) indicates the toxin is a pentapeptide with a similar structure to the heptapeptides and containing fi-methylaspartic acid, glutamic acid, arginine, dehydrobutyrine, and ADDA (MW 824). 

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