Tripeptide synthesis

Scheme 7.3 Efficient tripeptide synthesis employing various coupling reagents.

Lipases are also known to catalyze amide formation. Thus in 1987 Margolin and Klibanov [40] showed the use of porcine pancreatic lipase (PPL) for dipeptide synthesis in organic solvents. West and Wong [41] investigated several lipases and esterases for dipeptide and tripeptide synthesis, with variable yields observed. Later, Kawashiro et al. [42] also studied the dimerization of phenylalanine with PPL. 

Watts and Has well have demonstrated dipeptide and tripeptide synthesis, as the first example of EOF-based multistep s5mthesis, in a borosilicate glass microfluidic channel, as shown in Fig. 2. A T-shaped microreactor with... 

Watts and Haswell have demonstrated dipeptide and tripeptide synthesis, as the first example of EOF-based multistep synthesis, in a borosilicate glass microfluidic channel, as shown in Fig. 2. A T-shaped microreactor with 200pLmx50pLm channels was fabricated the overall reactor dimensions were 20 mm x 20 mm x 25 mm. The channels were filled with microporous silica frit to reduce hydrodynamic effects. After deprotection with one equivalent of hydrazine, tripeptide synthesis was also demonstrated. An offline high-pressure liquid chromatograph (HPLC) was used to determine the results of the synthesis. 

Kinetically controlled peptide synthesis synthesis ot bioactive peptides in organic solvent (dermorphin, enkephalin) amino acid oligomerization [22] di- and tripeptide synthesis with peptidomimetic leaving group [23-27]... 

Homologues of the classical papaya papain that have been tested for peptide S5mthesis are plant-derived enzymes such as bromelain and ficain. Bromelain extracted from pineapple could be applied in Met- and Leu-enkephalin synthesis in a low water system, reaching 97% yield [27]. Ficain isolated from Ficus glabrata latex was tested in di- and tripeptide synthesis in frozen water medium [23] and was used in the synthesis of Lys and Met oligomers starting from the respective ethyl esters [29]. 

Animal tissue is a soiuce of papain-related lysosomal cysteine peptidases that have been used in di- and tripeptide synthesis. Due to the insufficient homogenic preparations of cathepsin B, earlier reports of its synthetic activity have to be taken witii caution [16]. The availability of a recombinant production system for hiunan cathepsin B will allow experiments with pure enzyme. The endopeptidase cathepsin L from parasite Fasciola hepatica was expressed in yeast and used in the kinetically controlled synthesis of Cbz-Phe-Arg-Ser-NH starting from Cbz-Phe-Arg-OMe and H-Ser-NH in an aqueous medimn [31]. 

Di-and tripeptide synthesis in frozen aqueous medium synthesis of peptide isosters [30]... 

Boc-based tripeptide synthesis Yield (%) Fmoc-based tripeptide synthesis Yield (%)... 

The following short descriptions of the steps involved in the synthesis of a tripeptide will demonstrate the complexity of the problem amino acid units. In the later parts of this section we shall describe actual syntheses of well defined oligopeptides by linear elongation reactions and of less well defined polypeptides by fragment condensation. 

J.E. Baldwin (1975, 1976A) has developed a biomimetic synthesis which is loosely analogous to the biosynthetic pathway which starts with the so-called Amstein tripeptide. Baldwin used bicyclic dipeptides more suitable for stereoselective in vitro syntheses. 

Fig. 11. Use of D-amino acids in the synthesis of a hairpin loop portion from the CD4 receptor (a) all L-Ser—Lys—Ala tripeptide constmcted in the natural...

Cysteine [52-90 ] is a thiol-bearing amino acid which is readily isolated from the hydrolysis of protein. There ate only small amounts of cysteine and its disulfide, cystine, in living tissue (7). Glutathione [70-18-8] contains a mercaptomethyl group, HSCH2, and is a commonly found tripeptide in plants and animals. Coenzyme A [85-61-0] is another naturally occurring thiol that plays a central role in the synthesis and degradation of fatty acids. 

The IPNS enzyme has also been shown to recognize modified tripeptides. The synthesis of a range of tripeptides, other than aminoadipoyl cysteinyl valine (ACV) (Table 6), has given rise to a selection of modified penicillins using IPNS as a means of cyclizing the tripeptide (58). 

If you synthesized the tripeptide Leu-Phe-Ser from amino acids prepared by the Strecker synthesis, how many stereoisomers would you expect to be formed ... 

Describe the synthesis of the dipeptide Lys-Ala by Merrifield s solid phase chemical method of peptide synthesis. What pitfalls might be encountered if yon attempted to add a leucine residue to Lys-Ala to make a tripeptide ... 

An interesting new synthesis [Eq. (24)] of the tripeptide dl-phenylalanylphenylalanylglycine (38) from the oxazolone 39 has been reported. ... 

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... 

It is well known that native collagen containes tripeptide sequences, which alone are not capable of building up a triple helix (e.g. Gly-Pro-Leu, Gly-Pro-Ser) when they exist as homopolypeptides. The synthesis of threefold covalently bridged peptide chains opens up the possibility of investigating the folding properties of such weak helix formers, because the bridging reduces the entropy loss during triple-helix formation and thereby increases the thermodynamic stability of the tertiary structure. Therefore, we have... 

The synthesis of aldehydes and ketoamides was performed on solid phase as well as in solution (Scheme 2.2). A semicarbazone linker (6) was employed for the assembly of the aldehydes on solid phase whereas the corresponding aminoalcohol was coupled in solution to the tripeptide and oxidized to the aldehyde, which produced epimeric mixtures [137]. For the synthesis of the ketoamides, hydroxyester THP resins were used as solid support ((7), Scheme 2.2) [138]. In solution the peptide bond was formed using an aminohydroxycarboxylic acid building block [138, 147]. Oxidation of the free hydroxyl group yielded the final inhibitors ((8), Scheme 2.2). 

Griehl, C. and Merkel, S., Synthesis and separation of pprotected tripeptide epimers by RP-HPLC, Inti. J. Peptide Protein Res., 45, 217, 1995. 

Racemization studies in the synthesis of the tripeptide Z-Gly-Phe-Gly from Z-Gly-Phe and Gly-OC2H5 revealed that in THF at room temperature such racemization occurred to the extent of about 5%, in DMF at -10 °C, however, less than 0.5%. 53 103 In the synthesis of Boc-Val-Tyr-OC2H5 (50%) from Boc-Val and Tyr-OC2H5 with CDI, a small amount of 0-acylation of tyrosine (4%) also occurred in the dipeptide. 11] A V -Carbonyldibenzimidazole was found inferior to CDI in the synthesis of peptides because of poorer yields and more rigorous reaction conditions needed. 53... 

The amino acid, activated by uptake of SO3, reacts with a second molecule of amino acid to form the dipeptide, which can in turn react further to form a tripeptide (and so on). This peptide synthesis model, which is supported by experimental evidence, appeals because of its simplicity it may well correspond much more closely to conditions on the primeval Earth than do some other models (Chen and Yang, 2007). 

Tripeptides with N-terminal anthranilic acid part were used as starting materials in the solid-phase synthesis carried out on TentaGel resin to prepare 1,4,11,1 l -tetrahydro-2//-pyrazino[2,l-3]quinazoline-3,6-diones with various N-l and N-3 substituents <2003EPP1471066>. Tandem cyclization from [6+0] atom fragments took place in the solid-phase synthesis of 143 from 142. Intermediate 141 was built on bromoacetal resin (Scheme 17) <1998JOC3162>. 

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