Tetrapeptide derivative

Castro et al.117) have recently been able to show with the aid of structure-activity studies that tripeptide and tetrapeptide derivatives such as Boc-(3-Ala-Trp-Met-Asp-NH2 51 a from the C-terminal region of gastrin without phenylalanine as a gastrin antagonist inhibit in vivo the gastrin-stimulated acid secretion. 

The chloromethyl ketone of [D-Ala2,Leu5]enkephalin (DALECK) [66, 67] showed moderate preference for p receptors over 3 receptors in rat brain and was used for covalent labelling of opioid receptors [67, 68], Somewhat higher p selectivity was displayed by the tetrapeptide derivative H-Tyr-D-Ala-Gly-MePhe-CH2Cl (DAMK), which labelled irreversibly and selectively high-affinity p binding sites [69],... 

D. Seebach, M. Rueping, P. I. Arvidsson, T. Kimmerlin, P. Micuch, C. Noti, D. Langenegger, D. Hoyer, Linear, Peptidase-Resistant p /p -Di-and o/p -Tetrapeptide Derivatives with Nano-molar Affinities to a Human Somatostatin Receptor , Helv. Chem. Acta 2001,84,3503-3510. 

One-pot cyclooligomerization of the tetrapeptide derivative H-Ile-Ser-D-Val(Thz)-OH produces a novel series of constrained symmetrical macrocycles ryf/n-[-Ile-Ser-D-Val(Thz)-] , where n = 2-19, containing up to 19 thiazoles in the macrocycle <1999JA2603>. 

Haverstick DM, Cowan JF, Yatnada KM, Santoro SA. Inhibition of platelet adhesion to fibronectin, fibrinogen, and vcxi Willebrand Factor substrates by a synthetic tetrapeptide derived from the cell binding domain of fibrinectin. Blood 1985 66 946-952. 

A Boc-protected tetrapeptide derived from a sequence found in Philippine cobra venom has been reported to have weak antagonist activity at K receptors (807). Attachment of the C-terminal "address" sequence of [o-Ala ]-dynorphin A-d-lDNHg to this sequence resulted in a novel acetylated dynorphin A analog, JVA-901 (now referred to as venorphin). 

Substitutions for Gly" are well tolerated, particularly in the tetrapeptide derivatives. Sarcosine (NMeGly, Sar) at position 4 in tetrapeptide derivatives enhances opioid activity in antinociceptive assays (879). Substitution of Phe in position 4 of the tetrapeptide amide yields the dermorphin/enkephalin hybrid TAPP (T -D-Ala-Phe-PheNHa) (831), which is a potent p-selective agonist (see Table 7.18). This peptide can also be considered an analog of en-domorphin-2, although TAPP was synthesized several years before the discovery of the endo-... 

Incorporation of o-Arg in position 2 of dermorphin and tetrapeptide analogs yields peptides that are potent opioids in antinociceptive assays in mice (879,882). The tetrapeptide derivative Tyr-D-Arg-Phe-Sar (TAPS)is a potent opioid in antinociceptive assays and causes respiratory stimulation, rather than respiratory depression, that is antagonized by naloxonazine (883) TAPS also antagonizes the respiratory depression caused by dermorphin. On the basis of these results TAPS has been postulated to be a p-i agonist and a antagonist in vivo (883). In contrast, incorporation of L-Tic in position 2 of dermorphin converts the peptide to a 6-receptor antagonist (884). 

Tryptoquivalines appear to be tetrapeptides derived from tryptophan, an-thranilic acid, valine, and alanine (or methylalanine). Deoxynortryptoquivalone (FTN) may be the first metabolite formed in the pathway of tryptoquivaline biosynthesis. Oxidation of the secondary amine to the hydroxyamine would form nortryptoquivalone. If the isobutyl side chain from the above tryptoquivalones is lost by further oxidation, FTJ and FTE would result. On the other hand, if reduction of the carbonyl group following acetylation occurs on the side chain, nortryptoquivaline (FTD) or deoxynortryptoquivaline respectively, would be... 

Similarly, a 20-membered ring of a tetrapeptide derivative containing a 3-substituted cinnamic acid template was closed on a solid support [593]. This methodology was also applied in the synthesis of a small library (15 examples) of cyclic RGD mimics having a diverse array of amino acids, with a variety of ring sizes [594]. 

The enzyme s three-dimensional structure was determined by standard techniques. The structure of complexes between the enzyme and two tetrapeptide derivatives, Ac-Pro-Ala-Pro-PheOH and Ac-Pro-Ala-Pro-TyrOH, was also elucidated. Details of the interaction between these peptides and Streptomyces griseus protease A (SGPA) were carefully investigated, and the authors discussed the conformational changes occurring in the enzyme as a result of interactions with the substrate as well as possible catalytic mechanisms of this serine protease. 

After these results it seemed desirable to have at hand a tetrapeptide derivative of sequence 1-4 which would allow coupling of the glycine carboxyl to the sequence 5-27, with the P-carbojcyl of aspartic acid unprotected, so as to minimize cyclization to the imide under the alkaline conditions of the coupling step. The hydrazide derivative depicted in Figure 10 fulfilled these requirements. 

Enantioselective synthesis of (-)-Geissman-Waiss lactone, antituber-cular y-butyrolactones and tetrapeptide derivatives. Abstracts of Papers, 242nd ACS National Meeting and Exposition, Denver, Colorado, August 28-September 1, 2011, p. ORGN-112 ... 

In 2009, Miller et al. explored the extension of their studies using 7i-methyl histidine-containing peptides as nucleophilic catalysts for group transfer reactions to the mono-sulfonylation of myo-inositol derivatives by aryl sulfonyl chlorides. Catalyst screening identified tetrapeptide derivative 92 as being efficient for distinguishing the enantiotopic secondary alcohol groups at the 1- and 3-positions... 

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