Synthetic Study on Selenocystine-Containing Peptides.

Koide, Takao; Itoh, Hiromi; Otaka, Akira; Yasui, Hiroyuki; Kuroda, Masataka; Esaki, Nobuyoshi; Soda, Kenji; Fujii, Nobutaka

doi:10.1248/cpb.41.502

Cited by 79 publications

(79 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The addition of β-chloroalanine as shown in Scheme 1 to the reaction mixture produces selenocystine as a yellow crystal [42][43]. Selenocystine can then be reduced in situ with sodium borohydride and treated with p-methoxybenzyl chloride to produce the pMob protected derivative [42]. The α-nitrogen atom can then be protected with an Fmoc group by treating Se-pmethoxybenzyl selenocysteine with Fmoc-OSu to produce N-9-fluorenylmethoxycarbonylSe-4-methoxybenzylselenocysteine (Fmoc-Se(pMob)-OH).…”

Section: Synthesis Of Selenocysteine Derivativesmentioning

confidence: 99%

“…and is accompanied by side reactions [45][46][47]. Kenji Soda pioneered the use of the p-methoxybenzyl group for selenocysteine [42]. The 4-methoxybenzyl group (pMob) is much more acid labile than the benzyl protecting group.…”

Section: Synthesis Of Selenocysteine Derivativesmentioning

confidence: 99%

“…The 4-methoxybenzyl group (pMob) is much more acid labile than the benzyl protecting group. The pMob group can be removed by using a cleavage cocktail of TFA, m-cresol, thioanisole, and trimethylsilyl trifluomethansulfonate (TMSOTf) [42]. Trimethylsilyl bromide has also been used [29].…”

Section: Synthesis Of Selenocysteine Derivativesmentioning

confidence: 99%

See 2 more Smart Citations

Incorporation of Selenocysteine into Proteins Using Peptide Ligation

Hondal

2005

PPL

View full text Add to dashboard Cite

Expressed protein ligation has become a frequently used technique to insert non-standard amino acids into proteins. The technique has been adapted to insert selenocysteine residues in place of cysteine residue in proteins, taking advantage of the similarity in the chemistries of sulfur and selenium. This replacement can confer unique structural and catalytic properties to enzymes and proteins. The development of this technique also allows for naturally occurring selenoproteins to be produced semisynthetically. KeywordsSelenocysteine; expressed protein ligation; thioredoxin reductase; semisynthetic Selenium, the mysterious moon-metalThe Swedish chemist, J.J. Berzilius discovered the 34 th element of the periodic table in 1817 and named it after the Greek goddess of the moon, Selene [1]. It is wholly appropriate that he named this element after the moon-goddess, because selenium, like the moon, has remained mysterious to science until the modern eraThe biological role of selenium began to be realized when Schwarz discovered a dietary factor that was necessary to prevent liver necrosis in rats [2]. He called this mysterious nutritional requirement, "Factor 3". He then determined that this dietary factor was the trace element selenium. In the 1970's, Chinese scientists reported that selenium could prevent a childhood cardiomyopathy known as Keshan disease [3], much like vitamin C can prevent the onset of scurvy. Beck and Levander later showed that both influenza and coxsackie viruses accumulate genetic mutations when these viruses have infected animal hosts that are deficient in selenium or vitamin E [4][5]. Keshan disease is caused when coxsackie virus mutates to a more virulent strain in a host deficient in selenium. In the 1980's, it was discovered that selenium is the only trace element that is incorporated directly into proteins as part of the polypeptide chain. [6]. The incorporation of selenium into proteins, known as selenoproteins, is beginning to explain the important role that selenium plays in human health. A number of important examples can be cited. Selenium is vital to the function of the thyroid gland. The key enzyme in the thyroid gland, which converts thyroxin (T4) to triidothyronine (T3), contains selenium [7]. Selenium is absolutely essential to human male fertility because an enzyme in the testes containing selenium protects developing sperm from oxidative injury [8]. There has long been anecdotal evidence that selenium offers † This work was supported by grant GM070742-01 NIH Public Access Selenium and the split personality of the genetic codeMany of the health benefits of selenium can be explained by its incorporation into proteins as the "21 st " amino acid, selenocysteine [12][13]. This amino acid, though rare, is ubiquitous in all of the kingdoms of life being found in eukarya, prokarya, and archea [14][15]. Examples of selenocysteine-containing proteins are found in plants, fungi, mammals, bacteria, and fish [16]. Like the other standard proteinogenic amino acids, selenocysteine i...

show abstract

Section: Synthesis Of Selenocysteine Derivativesmentioning

confidence: 99%

Section: Synthesis Of Selenocysteine Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Incorporation of Selenocysteine into Proteins Using Peptide Ligation

Hondal

2005

PPL

View full text Add to dashboard Cite

show abstract

“…One problem with using Sec in solid-phase peptide synthesis (SPPS) is the requirement for using benzyl-type protecting groups for the selenol side-chain owing to the incompatibility of a trityl group (Trt) with this sidechain [4][5][6][7]. Benzyl (Bzl) and p-methoxybenzyl (Mob) protecting groups are difficult to remove and require harsh conditions, such as the use of hydrofluoric acid (HF), silyl-Lewis acids, or thiophilic heavy metals.…”

Section: Introductionmentioning

confidence: 99%

Studies on deprotection of cysteine and selenocysteine side‐chain protecting groups

Harris¹,

Flemer²,

Hondal³

2006

Journal of Peptide Science

102

113

View full text Add to dashboard Cite

Abstract:We present here a simple method for deprotecting p-methoxybenzyl groups and acetamidomethyl groups from the sidechains of cysteine and selenocysteine. This method uses the highly elecrophilic, aromatic disulfides 2,2 -dithiobis(5-nitropyridine) (DTNP) and 2,2 -dithiodipyridine (DTP) dissolved in TFA to effect removal of these heretofore difficult-to-remove protecting groups. The dissolution of these reagents in TFA, in fact, serves to 'activate' them for the deprotection reaction because protonation of the nitrogen atom of the pyridine ring makes the disulfide bond more electrophilic. Thus, these reagents can be added to any standard cleavage cocktail used in peptide synthesis.The p-methoxybenzyl group of selenocysteine is easily removed by DTNP. Only sub-stoichiometric amounts of DTNP are required to cause full removal of the p-methoxybenzyl group, with as little as 0.2 equivalents necessary to effect 70% removal of the protecting group. In order to remove the p-methoxybenzyl group from cysteine, 2 equivalents of DTNP and the addition of thioanisole was required to effect removal. Thioanisole was absolutely required for the reaction in the case of the sulfur-containing amino acids, while it was not required for selenocysteine. The results were consistent with thioanisole acting as a catalyst. The acetamidomethyl group of cysteine could also be removed using DTNP, but required the addition of >15 equivalents to be effective. DTP was less robust as a deprotection reagent. We also demonstrate that this chemistry can be used in a simultaneous cyclization/deprotection reaction between selenocysteine and cysteine residues protected by p-methoxybenzyl groups to form a selenylsulfide bond, demonstrating future high utility of the deprotection method.

show abstract

“…The spectral data of 15 were identical to the literature. 37 The purity was Optical resolution of 1, 2, 13, and 15. Racemic samples were obtained from DL-serine following the same synthetic procedures described above.…”

Section: H Nmr N-(9-fluorenylmethoxycarbonyl)-o-(p-toluenesulfonyl)-mentioning

confidence: 99%

Improved synthetic routes to the selenocysteine derivatives useful for Boc-based peptide synthesis with benzylic protection on the selenium atom

Shimodaira¹,

Iwaoka²

2016

Arkivoc

View full text Add to dashboard Cite

Selenocysteine (Sec) derivatives, i.e., Boc-Sec(MBn)-OH (1) and Boc-Sec(MPM)-OH (2), which are useful for chemical synthesis of selenopeptides, were obtained from L-serine in five steps with total yields of 73% and 74%, respectively. The enantiomeric excesses were confirmed to be >99% e.e. by optical resolution using a chiral column on HPLC. On the other hand, for the case of a Fmoc-protected Sec derivative, i.e., FmocSec(MPM)-OH, similar reactions resulted in low yields and partial racemization taking place.

show abstract

Synthetic Study on Selenocystine-Containing Peptides.

Cited by 79 publications

References 2 publications

Incorporation of Selenocysteine into Proteins Using Peptide Ligation

Incorporation of Selenocysteine into Proteins Using Peptide Ligation

Studies on deprotection of cysteine and selenocysteine side‐chain protecting groups

Improved synthetic routes to the selenocysteine derivatives useful for Boc-based peptide synthesis with benzylic protection on the selenium atom

Contact Info

Product

Resources

About