Pseudopeptide analogs

On the other hand, pseudopeptide analogs of the C-terminal tetrapeptide of gastrin U7b), such as (tert.butyloxycarbonyl)-L-tryptophyl-4 (CH2—NH)-L-leucyl-L-aspartyl-L-phenylalaninamide 51b, in which the amide linkage is replaced by the isosteric modification CH2—NH, are potent agonists of acid secretion. 

Figure 1. A pseudopeptide analog (top) of the leucokinin C-terminal pentapeptide Phe-Phe-Ser-Tip-Gly-NH2 (bottom) in which the amide bond (-C(O)-NH-) between the two phenylalanine residues is replaced by a reduced bond linkage (-CHjNH-) (1,18). (Reproduced with permission from ref. 1. Copyright 1993 Wiley Liss.)...

Sulfakinin Pseudopeptide Analogs. Pseudopeptide analog studies of the sulfakinins have focused on the replacement of the labile Tyr(SQ3H) moiety with a more stable chemical construct. The sulfate group is highly susceptible to hydrolytic cleavage under acidic conditions. 

Fig. B.19.1. Peptide nucleic acid (PNA) is a DNA analog in which the (deoxy)ribosephosphate backbone has been replaced by an artificial pseudopeptide.

Most synthetic DNA analogs represent logical departures from the natural structure. However, one of the most radical structural modifications of DNA to appear in the literature is peptide nucleic acid (PNA, Fig. 1), in which the sugar-phosphate backbone is abolished entirely in favor of a pseudopeptide. PNA was first reported by Nielsen et al. in 1991... 

The replacement of amide bonds by retro-in-verso amide replacements (71, 72) and other amide bond isosteres generates pseudopeptides (11). This process was first used to stabilize peptide hormones in vivo and later to prepare transition state analog (TSA) inhibitors. Systematic efforts to convert good in vitro inhibitors into good in vivo inhibitors became the driving force for further development of peptidomimetics. Figure 15.17 illustrates some of the peptide backbone modifications that have been made in an effort to increase bioavailability. Replacement of scissile amide (CONH) bonds with groups insensitive to hydrolysis (e.g., CHaNH) has been extensively practiced. Reviews of this work have appeared (11,73). Removal of the proton donors and... 

This section is organized along the four fundamental properties of proteins. Hie imdertaken efibrts are summarized to elucidate how effectively these concepts can be transferred to synthetic polymer systems by integrating peptides (and their synthetic analogs, i.e., pseudopeptides) into synthetic polymers (translation of bioconcepts toward polymer sciences). 

In this paper, we discuss pseudopeptide mimetic analogs that have been developed for selected insect neuropeptide families, including the insect kinins, sulfakinins, myosuppressins, and insect tachykinins. First members of these families were isolated from the cockroach or locust on the basis of their ability to either stimulate or inhibit contractions of the isolated cockroach/hindgut. Subsequently, these peptide families have been found in a range of insect species and associated with a variety of different physiological responses. The paper closes... 

NACHMAN ET AL. Pseudopeptide Mimetic Analogs of Insect Neuropeptides 211... 

The development of potent pseudopeptide and nonpeptide analogs will be greatly facilitated by a knowledge of the active conformation adopted by insect neuropeptide ligands at the receptor site. Most small peptides in aqueous solution are too flexible to allow researchers to gather information about conformational preferences via NMR and CD spectroscopic techniques. In order to circumvent this problem, flexibility must be limited by the introduction of conformational constraints. 

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