Evaluation of 4-tert-Butyl-Benzhydrylamine Resin (BUBHAR) as an Alternative Solid Support for Peptide Synthesis

Autor: Luiggi F. Salomoni, Clovis R. Nakaie, Luciana Malavolta, Sinval E. G. Souza, Shirley Schreier, Eduardo Maffud Cilli, Guita Nicolaewsky Jubilut
Přispěvatelé: Universidade Federal de São Paulo (UNIFESP), Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
International Journal of Polymer Science, Vol 2020 (2020)
ISSN: 1687-9422
DOI: 10.1155/2020/5479343
Popis: Made available in DSpace on 2020-12-12T02:24:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Following preliminary reports that introduced 4-Tert-butylbenzhydrylamine resin (BUBHAR) as a novel polymer for use in solid-phase peptide chemistry (SPPS), some physical-chemical properties of its structure, certainly relevant for its application in this methodology, were compared with those of the largely used methylbenzhydrylamine resin (MBHAR). In order to rule out possible MBHAR-related commercial source effects for SPPS, we initially compared MBHAR batches acquired from three different manufacturers with homemade BUBHARs. The bead solvation properties of these two resins in solvents used in the tert-butyl (Boc-based) SPPS technique indicated that the mean swelling values of these solid supports (% volume of solvated bead occupied by the solvent) were 51% and 67% for MBHAR and BUBHAR, respectively. This result strongly suggests a good potential for the latter polymer in terms of application for application in SPPS. In order to move forward with this approach, the synthesis of the carboxy-Terminal peptide fragment (Gln-Asn-Cys-Pro-(D-Arg)-Gly-Amide) of the antidiuretic hormone, desmopressin ([3-Mpa∗-Tyr-Phe-Gln-Asn-Cys-Pro-(D-Arg)-Gly-Amide], ∗1-[3-mercaptopropionic acid]), which our laboratory is producing routinely in large scale for the Health Secretary of Sao Paulo State. The comparative synthesis was conducted using these two resins with similar substitution degrees (0.7 mmol/g). In contrast to MBHAR, surprisingly no need for a GlnAsn recoupling reaction was observed when BUBHAR was used. This result might be due to improved solvation of the desmopressin C-Terminal Asn-Cys-Pro-(D-Arg)-Gly-segment when bound to this latter resin as observed by microscopic swelling degrees of peptide-resin beads and also by greater mobility detected of peptide chains within the BUBHAR polymer backbone. This finding was determined by comparative electron paramagnetic resonance (EPR) of both peptide resins attaching the amino acid-Type paramagnetic 2.2.6.6-Tetramethylpiperidine-1-oxyl-4-Amino-4-carboxylic acid (Toac) spin label early introduced by our group. Department of Biophysics Escola Paulista de Medicina Universidade Federal de Sao Paulo Department of Physiological Sciences Santa Casa de Sao Paulo School of Medical Sciences Department of Biochemistry and Chemistry Technology Institute of Chemistry Department of Biochemistry Institute of Chemistry Universidade de Sao Paulo
Databáze: OpenAIRE
Externí odkaz: