Peptide analog design

Von Geldern TW, Rockway TW, Davidsen SK, Budzik GP, Bush EN, Chu-Moyer MY, Devine EM Jr, Holleman WH, Johnson MC, Lucas SD, Pollock DM, Smital JM, Thomas AM, Opgenorth TJ. Small atrial natriuretic peptide analogs design, synthesis, and structural requirements for guanylate cyclase activation. J. Med. Chem. 1992 35 808-816. 

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... 

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,... 

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... 

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]. 

Furthermore, we believe that our hypothesis regarding design of antagonist analogs with prolonged activity offers a potentially useful approach to peptide drug design. 

The potential utility of peptides as therapeutic agents with clinical applications is limited as a consequence of intrinsic peptide properties such as metabolic instability or poor transmembrane mobility. Hence, the design and synthesis of meta-bolically stable peptide analogs that can either mimic or block the bioactivity of natural peptides or enzymes is an important area of medicinal chemistry research. Numerous structural modifications to peptides have been examined in pursuit of molecules with more desirable properties [1-3]. These modified structures, peptidomimetics, are nonpeptide molecules that imitate the desired properties of the natural substances. 

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