Peptide analogs

Solid phase peptide synthesis does not solve all purification problems however Even if every coupling step m the ribonuclease synthesis proceeded in 99% yield the product would be contaminated with many different peptides containing 123 ammo acids 122 ammo acids and so on Thus Memfield and Gutte s six weeks of synthesis was fol lowed by four months spent m purifying the final product The technique has since been refined to the point that yields at the 99% level and greater are achieved with current instrumentation and thousands of peptides and peptide analogs have been prepared by the solid phase method... 

Alternate ways to interfere with the orexin system may be via inhibition of dipeptidyl peptidases or proteolysis-resistant peptide analogs as shown for other peptides. This could prolong and boost orexinergic signaling. OX-A but not OX-B can enters the brain by simple diffusion via the blood-brain barrier. Abundance of orexins and their receptors in the olfactory bulb and throughout all parts of the central olfactory system may offer transnasal routes for drug application. 

Several reports have now shown that fluorescent-labeled polycationic / -peptides (a Tat (47-57) yS-peptide analog (165) [260] as well as homooligomers of y9 -HArg (166) [261] and of yS -HLys (167) [261, 262] with seven to eight residues) are also able to translocate rapidly across human cell membranes in a temperature-independent manner and to accumulate in the nucleus. 

Basu S., Wickstrom E. Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insu-lin-like growth factor 1 for increased cellular uptake. Bioconjug. Chem. 1997 8 481-488. 

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... 

Cathepsin D. The design of inhibitors of the aspartyl protease cathepsin D started from a virtual library of peptide analogs that contained the typical hydroxyethylamine isoster for the cleavable peptide bond. As the availability of starting materials would have generated a library of about 1 billion compounds, virtual screening was applied to reduce this multitude of candidate structures to a reasonable number. The backbone of a peptide... 

Schiller PW. Development of receptor specific opioid peptide analogs. In Ellis GP, West BG, eds. Progress in Medicinal Chemistry. Vol. 28. Amsterdam Elsevier, 1991 301-340. 

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. 

Wilkes BC, Schiller PW. Molecular dynamics simulations of opioid peptide analogs containing multiple conformational restrictions. Int J Peptide Protein Res 1992 40 249-254. 

Burdick D, Soreghan B, Kwon M, Kosmoski J, Rnauer M, Henschen A, Yates J, Cotman C, Glabe C. Assembly and aggregation properties of synthetic Alzheimer s A4/beta amyloid peptide analogs. J Biol Chem 1992 267 546-554. 

VHL Lee, DJ Schanzlin, RE Smith. (1986). Interaction of rabbit conjunctival mucin with tear protein and peptide analogs. In FJ Holly, ed. The Preocular Tear Film in Health, Disease, and Contact Lens Wear. Lubbock, TX Dry Eye Institute, pp 341-355. 

DTPA has also been used in the peptide-based " in-DTPA-octreotide. Octreotide is a shortened peptide analog of somatostatin designed to be more stable in vivo. Radiolabeling of octreotide for diagnostic imaging applications with radioisotopes for PET or SPECT has been investigated,... 

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

P. Kanellis, J. Yang, H. C. Cheung, and R. E. Lenkinski, Synthetic peptide analogs of skeletal troponin C Fluorescence studies of analogs of the low-affinity calcium-binding site II, Arch. Biochem. Biophys. 220, 530-540 (1983). 

The truncated peptide analogs were used to demonstrate the specificity of the method and to evaluate the limit of quantitation of potential impurities. Potential impurities were spiked into a solution of IB-367 at 0.05%, 0.1%, 0.2%, 0.5%, and 1% to assay the linearity of potential impurities at low concentrations. The method exhibited acceptable linearity for impurities from 0.05 to 1%. The relative response factors of these analogs were assessed to determine area normalization feasibility. 

In many of the direct amide oxidations illustrated above, the reactions were used to functionalize amino acid derivatives. Because of the reactions effectiveness in this area, anodic electrochemistry has proven to be an outstanding tool for building constrained peptidomimetics [78-81]. In this work, a series of constrained peptide analogs were designed by replacing spatially close hydrogens in a proposed... 

Figure 13.4 Various LSDl inhibitors. Suicide inactivators pargyline 5 and tranylcypromine 6. Histone H3 tail 21-amino acid peptide analogs 7-11 as reversible and irreversible inibitors. Noncompetitive polyamine inhibitors 12 and 13.

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]. 

A Fuertoes-Matei, J Li, KC Waldron. Micellar electrokinetic chromatographic study of interaction between enkephalin peptide analogs and charged micelles. J Chromatogr B 695 39-47, 1997. 

As discussed above, the development of peptide analogs with high potency requires an understanding of those features of structure and conformation which are critical for receptor binding and compatible with receptor transduction. Superpotency can result by maximizing the conformational and stereoelectronlc structural... 

Solution Conformation. Knowledge of solution conformation of constrained peptide analogs has proven very useful for corre-... 

S,4S)-4,8-Diamino-3-hydroxyoctanoic acid (DAHOA) derivatives were synthesized by the route shown in Scheme II using the known aldehyde Boc-Lys(Z)-CH0 (29) and were converted to the DAHOA peptide analogs shown. Inhibition of penicillopepsin by all statine and DAHOA pepstatin analogs was measured using substrate 21. The results of these determinations are shown in Table I. 

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