Navegando por Palavras-chave "methylbenzhydrylamine-resin"

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    Evaluation of the trifluoromethanosulfonic acid/trifluoroacetic acid/thioanisole cleavage procedure for application in solid-phase peptide synthesis
    (Pharmaceutical Soc Japan, 2001-09-01) Jubilut, Guita Nicolaewsky [UNIFESP]; Cilli, Eduardo Maffud [UNIFESP]; Tominaga, Mineko [UNIFESP]; Miranda, Antonio [UNIFESP]; Okada, Yoshio; Nakaie, Clovis Ryuichi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Kobe Gakuin Univ
    As an extension of our investigation of peptidyl-resin linkage stability towards different cleavage procedures used in the solid-phase peptide synthesis (SPPS) technique, the present paper evaluated the trifluoromethanesulfonic acid (TFMSA)/trifluoroacetic acid (TFA)/thioanisole method, varying the type of resin (benzhydrylamine-resin, BHAR; methylbenzhydrylamine-resin, MBHAR and 4-(oxymethyl)-phenylacetamidomethyl-resin, PAMR) and peptide resin-bound residue (Gly and Phe). the vasoactive angiotensin II (AII, DRVYIHPF) and its /Gly(8)/-AII analogue linked to those resins used routinely in tert-butyloxycarbonyl (Boc)-SPPS chemistry were submitted comparatively to a time course study towards TFMSA/TFA cleavage. At VC, /Gly(8)/-AII was completely removed from all resins in less than 6 h, but the hydrophobic Plies moiety-containing All sequence was only partially cleaved (not more than 15%) from BHAR or MBHAR in this period. At 25 degreesC, /Gly(8)/-AII cleavage time decreased to less than 2 h irrespective of the solid support. and quantitative removal of All from PAMR and MBHAR occurred in less than 3 h. However, about 10-15 h seemed to be necessary for cleavage of All from BHAR, and in this extended cleavage reaction a significant increase in peptide degradation rate was observed. Regardless of the cleavage temperature used, the decreasing order of acid stability measured for resins was BHAR > MBHAR > PAMR. Collectively, these findings demonstrated the feasibility of applying TFMSA/TFA solution as a substitute for anhydrous HF at the cleavage step in Boc-SPPS methodology. Care should be taken however, as the cleavage efficacy depends on multiple factors including the resin, peptide sequence. the time and temperature of reaction.
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    Novel Copoly(Styrene-Divinylbenzene)-Resins with Different Phenylmethylamine Groups for Use in Peptide Synthesis Method
    (Bentham Science Publ Ltd, 2015-01-01) Souza, Sinval Estevam Gregorio de [UNIFESP]; Malavolta, Luciana [UNIFESP]; Cilli, Eduardo Maffud [UNIFESP]; Schreier, Shirley [UNIFESP]; Jubilut, Guita Nicolaewsky [UNIFESP]; Nakaie, Clovis Ryuichi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Santa Casa Sao Paulo Sch Med Sci; Unesp; Universidade de São Paulo (USP)
    Differently than the 4-methylbenzhydrylamine-resin (MBHAR) which contains a methyl group coupled to the phenylmethylamine-functionalized copoly(styrene-divinilbenzene) structure, alternative resins containing the electron-donating 4-tert-butyl-(BUBHAR) or the electron-withdrawing 2-chloro-(ClBHAR) and 2,4-chloro-(diClBHAR) groups were developed as potential supports for carboxamide peptide synthesis. Initially, a time-course investigation of HF cleavage reaction (0 degrees C) with these resins bearing the vasoconstrictor angiotensin II (AngII, DRVYIHPF) or its Gly(8)-AngII analogue revealed that the peptide-BUBHAR linkage is much more labile than those with ClBHAR or diClBHAR. HF cleavage times of near 2 h or longer than 24 h were needed for complete removal of peptide chains from these two classes of resin, respectively. By including MBHAR and benzhydrylamine-resins (BHAR) in this comparative study, the decreasing order of acid stability of the peptidyl-resin linkage was diClBHAR > ClBHAR > BHAR > MBHAR similar to BUBHAR. The same stability order was observed for the HCl/ propionic acid hydrolysis reaction (130 degrees C) with the Phe-or Gly-resins. These findings thus suggest that ClBHAR and diClBHAR are not appropriate for use in peptide synthesis. Nevertheless, these supports could still be tested as stationary phases for affinity chromatography. When placed into more apolar solvents, the beads of all of these resins exhibited a greater swelling (as measured by a microscope) or higher mobility of the polymer matrix (as measured with EPR experiments using spin-labeled beads). Moreover, under the latter approach, BUBHAR displayed a comparatively higher solvation degree than did MBHAR (in DCM, DMF and NMP), with slightly higher peptide synthesis yields as well.
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    Resin selection based on the lability of peptidyl-resin linkage towards HF and TFA steps: Dependence on the C-terminal amino acid and peptide length
    (Pharmaceutical Soc Japan, 1999-11-01) Jubilut, Guita Nicolaewsky [UNIFESP]; Miranda, Maria Teresa; Tominaga, Mineko; Okada, Yoshio; Miranda, Antonio de [UNIFESP]; Nakaie, Clovis Ryuichi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Kobe Gakuin Univ
    Ideally, the solid support used for teut-butyloxycarbonyl (Boc)-peptide synthesis method must allow sufficient stability of the peptide linkage towards TFA-alpha-amino deprotection but adequate lability to final HF cleavage. Due to these conflicting characteristics, the choice of the correct resin for peptide synthesis is complex and dependent upon many factors. Aiming to clarify this issue, a time-course study of the trifluoroacetic acid (TFA) and HF steps using model peptidyl-resins was developed. The peptidyl-resin bond stability was strongly dependent upon the resin and the carboxy-terminus residue, The decreasing order of acid stability for resins was: benzhydrylamine-resin (BHAR)>p-methylbenzhydrylamine-resin (MBHAR)congruent to 4-(oxymethyl)-phenylacetamidomethyl-resin (PAMR)>chloromethyl-resin (CMR) and Phe>Gly congruent to His congruent to Asp for C-terminal amino acids. HF-cleavage times of near 6 h (BHAR) and 2-3 h (MBHAR and PAMR) were necessary for quantitative cleavage of hydrophobic Phe residue-containing sequence at its C-terminal portion. When premature chain loss in TFA and incomplete cleavage in HF values were both quantitatively considered, a significant decrease in the overall yield (up to 35%) was observed in some resins, Moreover, MBHAR was more suitable than BHAR only when the peptide C-terminal residue is hydrophohic. The data also allow the prediction that due to more significant chain loss in TFA when MBHAR is used, BHAR will be the resin of choice for much longer than 40-mer peptide sequences containing C-terminal hydrophilic residues. Otherwise PAMR is the best resin for the synthesis of free carboxyl peptides but significantly low HF cleavage was observed when the C-terminal amino acid is of the hydrophobic-type.