5-Selective dipeptides

Equilibrium Constants for Selected Dipeptide Chelate Complexes of Vanadate... 

H.J. Issaq, Separation of Selected Dipeptides by High Performance Liquid Chromatography, J. Liq. Chromatogr., 9(1)(1986)229. 

Relative P-turn formation potentials of selected dipeptides can be determined and compared with corresponding values of prediction codes. 

Saturation of the aromatic ring of pentopril analogues is also consistent with ACE inhibition as demonstrated by the oral activity of indolapril (23). The necessary heterocyclic component (21) can in principle be prepared by catalytic perhydrogenation (Rh/C, HOAc) of the corresponding indole. A single isomer predominates. The product is condensed by amide bond formation with the appropriate alanylhomophenylalanyl dipeptide ester 20 to give 22. Selective saponification to 23 could be accomplished by treatment with HCl gas. Use of the appropriate stereoisomers (prepared by resolution processes) produces chiral indolapril [8]. 

First, they compared CSPs 1 and 3 prepared by the two-step solid-phase methodology with their commercially available counterparts (CSPs 2 and 4) obtained by direct reaction of the preformed selector with a silica support. Although no exact data characterizing the surface coverage density for these phases were reported, all of the CSPs separated all four racemates tested equally. These results shown in Table 3-3 subsequently led to the preparation of a series of dipeptide and tripeptide CSPs 5-10 using a similar synthetic approach. Although the majority of these phases exhibited selectivities lower or similar to those of selectors built around a single amino acid (Table 3-3), this study demonstrated that the solid-phase synthesis was a... 

The addition of titanated 2-methylpropenamides to 2-(ter/-butoxycarbonylamino)a]dehydes was investigated during the synthesis of dipeptide isosteres and was shown to exhibit low selectivity only93,94. 

Substitution of a dipeptide unit by a cychc dipeptide derivative within a peptide chain can induce certain conformational restraints that may alter the biological response via changing receptor selectivity. A facile procedure for synthesis of pyrazinone ring-containing opioid mimetics [21] has been elaborated, based on the cycHzation of readily available dipep-tidyl chloromethyl ketones [22] (Scheme 6). This method affords 2(IH)-pyrazinone derivatives containing substituents with desired functional groups at positions 3 and 6 in high yield. 

For example, use of 10 different isocyanides and amines, along with 40 different aldehydes and carboxylic acids has the potential to generate 160,000 different dipeptide analogs.65 This system was explored by synthesizing arbitrarily chosen sets of 20 compounds that were synthesized in parallel. The biological assay data from these 20 combinations were then used to select the next 20 combinations for synthesis. The synthesis-assay-selection process was repeated 20 times. At the end of this process the average inhibitory concentration of the set of 20 products had been decreased from 1 mM to less than 11xM. 

Weber, S. G., Tsai, H., and Sandberg, M., Electrochemical detection of dipeptides with selectivity against amino acids, ]. Chromatogr., 638, 1, 1993. 

In order to identify tyrosine derivatives that would lead to polymers that are processible, mechanically strong, and also biocompatible, we initiated a detailed investigation of the structure-property relationships in polyiminocarbonates and polycarbonates. Since the amino and carboxylic acid groups of tyrosine dipeptide (the N and C termini) provide convenient attachment points, selected pendent chains can be used to modify the overall properties of the polymers. This is an important structural feature of tyrosine dipcptide derived polymers. 

In 1995 the dipeptide H-Dmt-Tic-OH was reported to be a 6-opioid antagonist with unprecedented 6-receptor affinity (K = 0.022 nM) and 6 receptor selectivity (Kf/Kf = 150,000) [47]. However, in a direct comparison under identical assay conditions, this compound showed about 30 times lower 6-antagonist potency and 6 times lower 6-receptor selectivity... 

Temussi PA, Salvadori S, Amodeo P, Bianchi C, Guerrini R, Tomatis R, Lazarus LH, Picone D, Tancredi T. Selective opioid dipeptides. Biochem Biophys Res Commun 1994 198 933-939. 

Page D, McClory A, Mischki T, Schmidt R, Butterworth J, St-Onge S, Labarre M, Payza K, Brown W. Novel Dmt-Tic dipeptide analogues as selective delta-opioid receptor antagonists. Bioorg Med Chem Lett 2000 10 167-170. 

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