Identification of amino acid thiohydantoins directly by thin-layer chromatography and indirectly by gas-liquid chromatography after hydrolysis. (1/24)

A method is described for the identification of amino acid thiohydantoins by two-dimensional t.l.c. An indirect method for the determination of amino acid thiohydantoins is described which, after hydrolysis, the corresponding amino acids are determined by g.l.c.  (+info)

Fluorous synthesis of hydantoins and thiohydantoins. (2/24)

[reaction: see text] A fluorous synthesis of hydantoins is introduced. The reaction of perfluoroalkyl (Rfh)-tagged amino esters with an isocyanate is followed by the cyclization of ureas and simultaneous cleavage of the fluorous tag to afford hydantoins. The product purification is performed by solid-phase extraction over FluoroFlash cartridges, and no fluorous solvent is involved in either the reaction or the separation processes. The same method applies to synthesis of thiohydantoins.  (+info)

Automated carboxy-terminal sequence analysis of peptides. (3/24)

Proteins and peptides can be sequenced from the carboxy-terminus with isothiocyanate reagents to produce amino acid thiohydantoin derivatives. Previous studies in our laboratory have focused on solution phase conditions for formation of the peptidylthiohydantoins with trimethylsilylisothiocyanate (TMS-ITC) and for hydrolysis of these peptidylthiohydantoins into an amino acid thiohydantoin derivative and a new shortened peptide capable of continued degradation (Bailey, J. M. & Shively, J. E., 1990, Biochemistry 29, 3145-3156). The current study is a continuation of this work and describes the construction of an instrument for automated C-terminal sequencing, the application of the thiocyanate chemistry to peptides covalently coupled to a novel polyethylene solid support (Shenoy, N. R., Bailey, J. M., & Shively, J. E., 1992, Protein Sci. I, 58-67), the use of sodium trimethylsilanolate as a novel reagent for the specific cleavage of the derivatized C-terminal amino acid, and the development of methodology to sequence through the difficult amino acid, aspartate. Automated programs are described for the C-terminal sequencing of peptides covalently attached to carboxylic acid-modified polyethylene. The chemistry involves activation with acetic anhydride, derivatization with TMS-ITC, and cleavage of the derivatized C-terminal amino acid with sodium trimethylsilanolate. The thiohydantoin amino acid is identified by on-line high performance liquid chromatography using a Phenomenex Ultracarb 5 ODS(30) column and a triethylamine/phosphoric acid buffer system containing pentanesulfonic acid. The generality of our automated C-terminal sequencing methodology was examined by sequencing model peptides containing all 20 of the common amino acids. All of the amino acids were found to sequence in high yield (90% or greater) except for asparagine and aspartate, which could be only partially removed, and proline, which was found not be capable of derivatization. In spite of these current limitations, the methodology should be a valuable new tool for the C-terminal sequence analysis of peptides.  (+info)

Fluorous parallel synthesis of a hydantoin/thiohydantoin library. (4/24)

Fluorous tagging strategy is applied to solution-phase parallel synthesis of a library containing hydantoin and thiohydantoin analogs. Two perfluoroalkyl (Rf)-tagged alpha-amino esters each react with six aromatic aldehydes under reductive amination conditions. Twelve amino esters then each react with 10 isocyanates and isothiocyanates in parallel. The resulting 120 ureas and thioureas undergo spontaneous cyclization to form the corresponding hydantoins and thiohydantoins. The intermediate and final product purifications are performed with solid-phase extraction (SPE) over FluoroFlash cartridges, no chromatography is required. Using standard instruments and straightforward SPE technique, one chemist accomplished the 120-member library synthesis in less than five working days, including starting material synthesis and product analysis.  (+info)

EM49, a new peptide antibiotic IV. The structure of EM49. (5/24)

EM49 is a family of similar peptide antibiotics, each an octapeptide acylated with a beta-hydroxy fatty acid. This paper described the determination of the structure of the fatty acyl residue, the selective removal of this residue from the peptide portion of the molecule, and the sequential analysis of the peptide by the EDMAN method. The structure of EM49, 1, is derived by this degradation.  (+info)

A simple synthesis of 2-thiohydantoins. (6/24)

2-Thiohydantoin derivatives are produced by heating a mixture of thiourea and an alpha-amino acid. The method described offers the advantages of simplicity, low cost, easy work-up and scalability.  (+info)

Reactivity of 2-thiohydantoins towards various electrophilic reagents: applications to the synthesis of new 2-ylidene-3,5-dihydro-4H-imidazol-4-ones. (7/24)

A new route to 5-(imidazolidin-2-ylidene)-2-methylsulfanyl-3,5-dihydro-imidazol-4-ones 4a-c using ketene dithioacetal intermediates 3a-c is described. The reactivity of thiohydantoin derivatives 2a-c towards N,N-dimethylformamide diethylacetal (DMF-DEA) was also explored using solvent-free technique under microwave irradiation (mu omega). The (1)H- and (13)C-NMR spectra of some representative products are discussed.  (+info)

Discovery of an orally-active nonsteroidal androgen receptor pure antagonist and the structure-activity relationships of its derivatives. (8/24)

The 3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethylthiohydantoin derivatives which have carboxy-terminal side chains were synthesized and their agonistic/antagonistic activities against androgen receptor (AR) measured. Among them, compound 13b showed antagonistic activity (IC50=130 nM) with no agonistic activity even at 10000 nM. This compound exhibited significant metabolic stability and oral antiandrogenic activity (ED50=7 mg/kg).  (+info)

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