Modified amino adds

The development of chiral peptide-based metal catalysts has also been studied. The group of Gilbertson has synthesized several phosphine-modified amino adds and incorporated two of them into short peptide sequences.[45J,71 They demonstrated the formation of several metal complexes, in particular Rh complexes, and reported their structure as well as their ability to catalyze enantioselectively certain hydrogenation reactions.[481 While the enantioselectivities observed are modest so far, optimization through combinatorial synthesis will probably lead to useful catalysts. The synthesis of the sulfide protected form of both Fmoc- and Boc-dicyclohexylphosphinoserine 49 and -diphenylphosphinoserine 50 has been reported, in addition to diphenylphosphino-L-proline 51 (Scheme 14).[49 To show their compatibility with solid-phase peptide synthesis, they were incorporated into hydrophobic peptides, such as dodecapeptide 53, using the standard Fmoc protocol (Scheme 15).[451 For better results, the phosphine-modified amino acid 50 was coupled as a Fmoc-protected dipeptide 56, rather than the usual Fmoc derivative 52.[471 As an illustrative example, the synthesis of diphe-nylphosphinoserine 52 is depicted in Scheme 16J45 ... 

The polypeptide of type-L isozyme is composed of 916 amino acid residues. There are two covalently modified amino adds about one-fourth of the amino-terminal threonines are blocked by an acetyl group, and a lysyl residue (Lys762) is linked to the cofactor pyridoxal-P. The partial amino-terminal acetylation appeared to be a natural feature of type-L isozyme, and both the blocked and unblocked forms of type-L phosphorylase may exist in potato tubers. 

Common posttranslational modifications of proteins. Frequently modified amino adds for each moiety are described. Most modifications involve low-mass substituents (<500amu), but some modifications are small polypeptides of considerable mass such as ubiquitin or highly related peptide isomers like SUMO-1, SUMO-2, and SUMO 3. SUMO is the abbreviation for similar to ubiquitin methyl organizer , SUMO has different family members (SUMO 1, 2, and 3 that can combine with proteins). 

Modified amino acids that duplicate or mimic PTMs of proteins provide a useful means for studying in vivo structures, functions and regulations of proteins. Since recombinant proteins are not postlranslationally modified, introductions of the modified amino adds to duplicate postlranslationally modified proteins are invaluable to functional... 

NRPSs have made significant advances in the synthesis of cyclic polypeptides and the ability to introduce modified amino adds will assist in the development of scaffolds for biomaterials. However, NRPSs produce low molecular weight polypeptides and require large enz)nnatic complexes, which are difficult to use in large-scale production of polypeptides. 

All these peptides containing several heterocyclic systems derive from modified amino adds whose linkages have raised difficult problems of stereochemistry. In the case of amino acids containing a thiazole, a general... 

The Michael addidon of nitto compounds is a useful method for the preparadon of various naniral products The Michael kldidon of nittoalkanes to dehydroalanines gives ynitto-ct-amino acids, which provides a convenient synthesis of side-chain modified ct-amino acids fEq 4 114 " Transformadons of Y-nitto-ct-amino acid derivadves into ct-amino adds occur by... 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cy-doaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the 1-oxa-l,3-butadiene moiety in 2-816. The formed spirocydic ketones 2-818/2-819 can be used in natural products synthesis and in medidnal chemistry [410]. They have also been used in the preparation of exotic amino adds these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

Artificial hydrothermal vents might be constructed and supplied with plausible concentrations of simple reactants such as CO, H2, NH3, and H2S. Appropriate levels of amino adds induding a small chiral excess, along with the sorts of amphiphilic molecules described above, can be rationalized by the findings from the Murchison meteorite. Organic molecules such as found in irradiated interstellar ice models, including HMT, can also be induded. The system should indude weathered feldspars, which can be modified to indude the reduced transition-metal minerals that they are known to contain. [134] Such minerals as Fe,Ni sulfides are likely to have been both present and stable in the environment of early Earth and are known [153, 155] to catalyze formation of organic molecules from simpler precursors. 

Disulfide connectivities of a partially reduced and alkylated peptide can be identified by the pairwise recognition of the specifically derivatized PTH-Cys on sequencing/46 PTH-Cys(Cam) and PTH-Cys(CM) are reported to elute on the ABI sequencer with PTH-Glu and PTH-Ser, respectively/46 and PTH-Cys(NEM) after PTH-Pro. 49 Therefore, it is important to know the primary structure of the target molecule in advance and to focus on the determination of its disulfide arrangement during sequence analysis in order to avoid mis-assignment of the amino adds at the cycles of the modified cysteine residues. 

Asymmetric hydrogenations have been reported with palladium on silk 123>, palladium on modified cellulose 124> and on modified ion exchange resins 125 >. Also with Raney Nickel modified with amino adds 126> and peptides, 27>. Platinum-carbon catalysts exhibiting shape selectivity have been made by coating them with a thermosetting resin, which is carbonized. In such a way an organic molecular sieve skin is formed over the original catalyst 128>. 

More yS-amino acids are, apparently, special building blocks within natural (cyclo)peptides and depsipeptides [11]. It is not dear whether Nature aimed at an increase of proteolytic stability or at conformational modification. Chemists, however, followed this example of natural / -amino acid chemistry decades ago and started to modify known a-peptides by substitution of solitary a-amino adds with p-amino acids [12]. One major issue of this synthetic analoging was to increase the proteolytic stability of peptides [13, 14] with regard to peptidases [15]. A second goal was the controlled conformational tuning of cyclo-a-peptides with / -amino acid modifications. 

In Figure 1 we see baseline resolution of all the PTH amino adds in the standard. Roughly eqmvalent recoveries of all are noted, with the exception of His and Arg, which are somewhat broader in this system. Peak heights are equivalent to those found by manual iiyection of dilutions from a concentrated stock of PTH-AA. This indicates that no drastic losses were encountered with the use of 2% acetonitrile to redissolve the sample after R4 conversion and drying. Espedally noteworthy are the recoveries of PTH-Ser and PTH-Thr, despite the lack of DTT in the modified R4 and S4. One possibility is ihat the presence of DTT in the X2 wash of the flask between iixjections is a satisfactory substitution for inclusion in S4 and R4 for sequendng at this level. 

As stated earlier, only classical amino acids are built into polypeptides during amino acid polymerization, Howe er, other amino adds, classical amino acids that have been modified after incorporation into the chain, are found in proteins. >ome of the modified amino acids found in proteins are listed in Table 1.4. Vitamins ate required for the synthesis of some of the modified amino acids. For example, vitamin C is required for conversion of proiine to hydroxyproline. This and other vitamin cofactors are listed in Table T4. 

Modified amino acids that are not part of polypeptides may be formed by modification of one of the classical amino adds. Among the many examples of this type of modified amino acid are creatine (a modified form of glycine), ornithine... 

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